Use of corticotropin releasing factor antagonists and related compositions

ABSTRACT

The present invention relates to compositions and methods of achieving a therapeutic effect including, the treatment or prevention of Syndrome X in an animal, preferably a mammal including a human subject or a companion animal, using a corticotropin releasing factor (CRF) antagonist alone or together with a glucocorticoid receptor antagonist.

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application claims priority from co-pending ProvisionalApplication No. 60/162,340 filed Oct. 29, 1999.

BACKGROUND OF THE INVENTION

[0002] The present invention relates to compositions and methods ofachieving a therapeutic effect, including the treatment or prevention ofSyndrome X, in an animal, preferably a mammal, including a humansubject, and a companion animal, using a corticotropin releasing factor(CRF) antagonist alone or together with a glucocorticoid receptor (GR)antagonist.

[0003] Syndrome X, also known as metabolic syndrome, plurimetabolicsyndrome or insulin resistance syndrome, encompasses a complex ofdisturbances of carbohydrate and fat metabolism characterized byobesity, dyslipoproteinemia (low HDL and high LDL, VLDL andtriglycerides), hyperinsulinemia, insulin resistance, glucoseintolerance and hypertension (Atherosclerosis X, F. P. Woodford, J.Davignon, A. Sniderman (Eds.), Elsevier Science BV, Amsterdam (1995):520-524.). Syndrome X is associated with an elevated risk forcardiovascular disease.

[0004] There are striking similarities between Cushing's disease andSyndrome X, both being characterized by visceral obesity, hypertension,insulin resistance, glucose intolerance and hyperlipidemia (EndocrineResearch, 22(4), 701-708 (1996)). Cushing's disease is caused byhypersecretion of cortisol, the most important human glucocorticoid, bythe adrenal cortex. Cortisol is known to cause visceral fat accumulationand insulin resistance (Pennington Cent. Nutr. Ser. (1996), 5 (Molecularand Genetic Aspects of Obesity), 340-352; Nutrition, 13:795-803 (1997);and Prog. Obes. Res., 7:505-510 (1996)). Cortisol promotes hepaticgluconeogenesis and glycogen deposition and increases blood glucoselevels. Cortisol also increases the sensitivity of adipose tissue tolipolytic hormones, elevating fatty acid levels and thereby stimulatingtriglyceride synthesis and VLDL (very low density lipoprotein)secretion. The VLDL is converted to VLDL remnants or LDL (low densitylipoprotein) which are largely taken up by the liver via the LDLreceptors, resulting in down-regulation of the LDL receptor andconsequently hypertriglyceridemia and hyper-apobetalipoproteinemia.Abnormalities of glucocorticoid secretion and sensitivity in men havebeen shown to be associated with hypertension and insulin resistance(Endocrine Research, 22(4), 701-708 (1996); and Hypertension,1998;31:891-895). Hypersecretion of cortisol is the result of excessivesecretion of ACTH (adrenocorticotropic hormone). Administration of ACTHhas been shown to increase blood pressure in animals (J. Hypertension,16:593-600 (1998)). The secretion of ACTH is controlled by the releasinghormone, corticotropin releasing factor (CRF or CRH). Thus, a CRF (CRH)antagonist, by decreasing ACTH secretion, will amelioralte thehypersecretion of glucocorticoids and thereby be of therapeutic benefitin the treatment of Syndrome X.

[0005] In addition, the levels of glucocorticoids present in the bodyare primarily, but not solely, determined by the concentration of CRF,so the use of a combination of a CRF antagonist and a GR antagonist willbe of greater therapeutic benefit in the treatment of Syndrome X thanthe use of a CRF antagonist alone.

[0006] International Patent Application Publication No. WO 97/25042,published Jul. 17, 1997, discloses methods for the treatment and/orprophylaxis of Syndrome X by the administration of an agonist of PPARαand PPARγ, or a pharmaceutically acceptable derivative thereof, to ahuman or non-human animal in need of such treatment.

[0007] International Patent Application Publication No. WO 99/17761,published Apr. 15, 1999, discloses the use of nordihydroguaiaretic acidto treat or ameliorate the characteristic manifestations of Syndrome Xin a non-diabetic animal with normal serum glucose levels.

[0008] CRF antagonists are disclosed in U.S. Pat. Nos. 4,605,642 and5,063,245. They are also disclosed in International patent publicationsWO 95/33750; WO 95/34563; WO 94/13661; WO 94/13644; WO 94/13643; WO94/13676; WO 94/13677; WO 95/33727; WO 98/05661; WO 98/08847; WO98/08846; and European patent publications EP 778277 and EP 773023. CRFantagonists are also disclosed in the following patent publications: EP576350; EP 659747; EP 812831; WO 95/10506; WO 96/35689; WO 96/39400; WO97/00868; WO 97/14684; WO 97/29109; WO 97/29110; WO 97/35539; WO97/35580; WO 97/35846; WO 97/44038; WO 97/45421; WO98/03510; WO98/08821; WO 98/11075; WO 98/15543; WO 98/21200; WO 98/27066; WO98/29397; WO 98/29413; WO 98/42699; WO 98/35967; WO 98/42706; WO98/45295; WO 98/47874; WO 98/47903; WO 98/51312; WO 99/01454; WO99/01439; WO 99/10350; WO 99/12908; WO 99/00373; WO 99/38868; WO99/51597; WO 99/51599; WO 99/40089; WO 99/51598; and WO 99/51600. Theyare also disclosed in U.S. Pat. Nos. 5,109,111; 5,132,111; 5,245,009;5,464,847; 5,493,006; 5,510,458; 5,644,057; 5,663,292; 5,668,145;5,705,646; 5,712,303; and 5,723,608. An overview of the patentliterature on CRF antagonists is provided in T. E. Christos and A.Arvanitis, Exp. Opin. Ther. Patents (1998) 8(2):143-152.

[0009] The importance of CRF antagonists is set out in the literature,e.g., P. Black, Scientific American: “Science & Medicine,” 1995,2:16-25; T. Lovenberg, et al., Current Pharmaceutical Design, 1995, 1:305-316; D. T. Chalmers et al., Trends in Pharmacological Sciences,April 1996, pages 166-172; and U.S. Pat. No. 5,063,245. An outline ofthe activities possessed by CRF antagonists is found in M. J. Owens etal., 1991, Pharm. Rev., 43:425-473. CRF antagonists are described in theart as being effective in the treatment of stress-related illnesses,mood disorders such as depression, major depressive disorder, singleepisode depression, recurrent depression, child abuse induceddepression, postpartum depression, dysthemia, bipolar disorders, andcyclothymia; chronic fatigue syndrome; eating disorders such as anorexiaand bulimia nervosa; generalized anxiety disorder; panic disorder;phobias; obsessive-compulsive disorder; post-traumatic stress disorder;pain perception such as fibromyalgia; headache; gastrointestinaldiseases; hemorrhagic stress; ulcers; stress-induced psychotic episodes;fever; diarrhea; post-operative ileus; colonic hypersensitivity;irritable bowel syndrome; Crohn's disease; spastic colon; inflammatorydisorders such as rheumatoid arthritis and osteoarthritis; pain; asthma;psoriasis; allergies; osteoporosis; premature birth; hypertension,congestive heart failure; sleep disorders; neurodegenerative diseasessuch as Alzheimer's disease, senile dementia of the Alzheimer's type,multiinfarct dementia, Parkinson's disease, and Huntington's disease;head trauma; ischemic neuronal damage; excitotoxic neuronal damage;epilepsy; stroke; spinal cord trauma; psychosocial dwarfism; euthyroidsick syndrome; syndrome of inappropriate antidiuretic hormone; obesity;chemical dependencies and addictions; drug and alcohol withdrawalsymptoms; infertility; cancer; muscular spasms; urinary incontinence;hypoglycemia and immune dysfunctions including stress induced immunedysfunctions, immune suppression and human immunodeficiency virusinfections; and stress-induced infections in humans and animals.

[0010] GR antagonists are disclosed in the following references:International patent application PCT/IB00/00366, filed Mar. 27, 2000,and assigned to the assignee hereof; International patent publicationsWO 99/41256 and WO 99/41257; U.S. Pat. No. 5,696,127; European patentpublication 188396; European patent publication 683172; Internationalpatent publication WO 98/26783; International patent publication WO98/27986; International patent publication WO 98/31702; European patentpublication 903146; and International patent publications WO 99/41256and WO 99/41257.

[0011] GR modulators (e.g., agonists, partial agonists, antagonists andpartial antagonists) can be used in the treatment of diseases associatedwith an excess or a deficiency of glucocorticoids in the body. As such,they may be used to treat the following: obesity, diabetes,cardiovascular disease, hypertension, Syndrome X, depression, anxiety,glaucoma, human immunodeficiency virus (HIV) or acquiredimmunodeficiency syndrome (AIDS), neurodegeneration (for example,Alzheimer's and Parkinson's), cognition enhancement, Cushing's Syndrome,Addison's Disease, osteoporosis, frailty, inflammatory diseases (such asosteoarthritis, rheumatoid arthritis, asthma and rhinitis), tests ofadrenal function, viral infection, immunodeficiency, immunomodulation,autoimmune diseases, allergies, wound healing, compulsive behavior,multi-drug resistance, addiction, psychosis, anorexia, cachexia,post-traumatic stress syndrome, post-surgical bone fracture, medicalcatabolism and prevention of muscle frailty.

[0012] All of the hereinabove and below cited U.S. patents, U.S. patentapplications, published European patent applications and published PCTinternational patent applications are incorporated herein by referencein their entirety.

SUMMARY OF THE INVENTION

[0013] The present invention provides methods of treating or preventingSyndrome X in an animal which comprises administering to said animal anamount of a corticotropin releasing factor antagonist. Moreparticularly, the present invention provides these methods wherein atherapeutically effective amount of a corticotropin releasing factorantagonist is administered. More particularly, the present inventionprovides these methods wherein the corticotropin releasing factorantagonist is a compound of a particular generic formula as describedbelow.

[0014] Also, the present invention provides methods of treating orpreventing Syndrome X in an animal which comprises administering to saidanimal an amount of a corticotropin releasing factor antagonist and anamount of a glucocorticoid receptor antagonist; wherein the amount ofthe corticotropin releasing factor antagonist and the amount of theglucocorticoid receptor antagonist result in a therapeutic effect. Moreparticularly, the present invention provides these methods wherein thecorticotrophin releasing factor antagonist is a compound of a particulargeneric formula as described below. More particularly, the presentinvention provides these methods wherein the glucocorticoid receptorantagonist is a compound of formula IA wherein the variables are asdefined below.

[0015] Also, the present invention provides pharmaceutical compositionsfor treating or preventing Syndrome X which comprises an amount of acorticotropin releasing factor antagonist and a pharmaceuticallyacceptable vehicle, carrier or diluent. More particularly, the presentinvention provides these compositions which comprise a therapeuticallyeffective amount of a corticotropin releasing factor antagonist. Moreparticularly, the present invention provides these compositions whereinthe corticotropin releasing factor is a compound of a particular genericformula as described below.

[0016] Also, the present invention provides pharmaceutical compositionsfor treating or preventing Syndrome X which comprises an amount of acorticotropin releasing factor antagonist, an amount of a glucocorticoidreceptor antagonist and a pharmaceutically acceptable vehicle, carrieror diluent; wherein the amount of the corticotropin releasing factorantagonist and the amount of the glucocorticoid receptor antagonistresult in a therapeutic effect. More particularly, the present inventionprovides these compositions wherein the corticotrophin releasing factorantagonist is a compound of a particular generic formula as describedbelow. More particularly, the present invention provides thesecompositions wherein the glucocorticoid receptor antagonist is acompound of formula IA wherein the variables are as defined below.

[0017] Also, the present invention provides kits which comprise anamount of a corticotropin releasing factor antagonist and apharmaceutically acceptable vehicle, carrier or diluent in a first unitdosage form; an amount of a glucocorticoid receptor antagonist and apharmaceutically acceptable vehicle, carrier or diluent in a second unitdosage form; and a container for containing said first and second dosageforms; wherein the amount of the corticotropin releasing factorantagonist and the amount of the glucocorticoid receptor antagonistresult in a therapeutic effect. More particularly, the present inventionprovides these kits wherein the corticotrophin releasing factorantagonist is a compound of a particular generic formula as describedbelow. More particularly, the present invention provides these kitswherein the glucocorticoid receptor antagonist is a compound of formulaIA wherein the variables are as defined below.

[0018] The present invention relates to compositions and methods usefulin achieving therapeutic effects, such as the treatment or prevention ofSyndrome X, which compositions preferably comprise a corticotropinreleasing factor (CRF) antagonist alone or in combination with aglucocorticoid receptor (GR) antagonist, and a pharmaceuticallyacceptable carrier, vehicle or diluent, and which methods preferablycomprise administering to an animal, preferably a mammal including ahuman subject or a companion mammal in need of such treatment, a CRFantagonist and a GR antagonist.

[0019] The terms “treating” and “treatment,” as used herein, unlessotherwise indicated, include, inter alia, palliative and curativetreatment of any disorder enumerated within the methods of the presentinvention.

[0020] The terms “preventing,” “prevention” and “prophylaxis,” as usedherein, unless otherwise indicated, include the inhibition or preclusionof the development of any disorder enumerated within the methods of thepresent invention.

DETAILED DESCRIPTION OF THE INVENTION

[0021] Syndrome X is the syndrome characterized by an initial insulinresistant state, generating hyperinsulinaemia, dyslipidaemia andimpaired glucose tolerance, which can progress to non-insulin dependentdiabetes mellitus (Type II diabetes), characterized by hyperglycaemiaand which then further progresses to diabetic complications.

[0022] CRF antagonists alone or together with GR antagonists areeffective for the treatment and/or prophylaxis of Syndrome X and theresulting complications thereof. These compounds are thereforeconsidered to be useful for the treatment and/or prophylaxis of anycombination of the following list of disorders associated with SyndromeX and the resulting complications thereof, including, for example,insulin resistance, diabetes, more particularly non-insulin dependentdiabetes mellitus (Type II diabetes), and the complications associatedwith diabetes, dyslipidaemia, hyperinsulinaemia, hyperglycaemia,atherosclerosis, hypertension, cardiovascular disease and obesity. Thislist is for purposes of illustration only and is not intended to limitthe scope of the present invention.

[0023] The complications associated with diabetes include, for example,cardiovascular disease, especially atherosclerosis, retinopathy,neuropathy and renal disease including diabetic nephropathy,glomerulonephritis, glomerular sclerosis, nephrotic syndrome,hypertensive nephrosclerosis and end stage renal disease.

[0024] The term corticotropin releasing factor (CRF) antagonist refersto a compound having the ability to inhibit or reverse the deleteriouseffects of the presence of CRF. It is well known that CRF profoundlystimulates the pituitary-adrenalcortical axis and, in dysfunctionalstates, initiates behavioral, physiological and endocrine responses thatare essentially identical to those observed when animals, includinghumans and companion animals, are subjected to a stressful environment.Therefore, CRF antagonists are known to have utility, inter alia, in theamelioration of certain stress-induced conditions including memory loss,mood alteration, depression, hypertension and the like.

[0025] Any CRF antagonist can be used to practice the present invention,including those that are described in U.S. Pat. Nos. 4,605,642 and5,063,245; International patent publications WO 95/33750; WO 95/34563;WO 94/13661; WO 94/13644; WO 94/13643; WO 94/13676; WO94/13677; WO95/33727; WO 98/05661; WO 98/08847; and WO 98/08846; and European patentpublications EP 778277; and EP 773023. They also include those of thefollowing patent publications: EP 576350; EP 659747; EP 812831; WO95/10506; WO 96/35689; WO 96/39400; WO 97/00868; WO 97/14684; WO97/29109; WO 97/29110; WO 97/35539; WO 97/35580; WO 97/35846; WO97/44038; WO 97/45421; WO 98/03510; WO 98/08821; WO 98/11075; WO98/15543; WO 98/21200; WO 98/27066; WO 98/29397; WO 98/29413; WO98/42699; WO 98/35967; WO 98/42706; WO 98/45295; WO 98/47874; WO98/47903; WO 98/51312; WO 99/01454; WO99/01439; WO99/10350; WO99/12908;WO99/00373; WO 99/38868; WO 99/51597; WO 99/51599; WO 99/40089; WO99/51598; and WO 99/51600. They are also disclosed in U.S. Pat. Nos.5,109,111; 5,132,111; 5,245,009; 5,464,847; 5,493,006; 5,510,458;5,644,057; 5,663,292; 5,668,145; 5,705,646; 5,712,303; and 5,723,608.Additional information relating to preparing certain of these compoundsis provided in WO 96/39388, which describes the production of certainintermediates. As noted above, the texts of all of these publicationsare incorporated by reference herein in their entireties.

[0026] Following are listed particular examples of CRF antagonists thatmay be used in practicing the invention. It is understood that in thegeneric formulae employed below, the variables employed, e.g., “A”, “B”,“R₁”, “R₂”, etc. have the meanings attributed to them only in theparticular Roman numeral section in which they are found. Thus, themeaning attributed, for example, to “R¹” is different for the structuresin section I and the structures of the other sections.

[0027] I. For example, the CRF antagonist may be of the followingformula, described in WO 94/13677:

[0028] and the pharmaceutically acceptable acid addition salts thereof,wherein

[0029] A is NR₁R₂, CR₁R₂R₁₁, or C(═CR₁R₁₂)R₂, NHCR₁R₂R₁₁, OCR₁R₂R₁₁,SCR₁R₂R₁₁, NHNR₁R₂, CR₂R₁₁NHR₁, CR₂R,₁₁OR₁, CR₂R₁₁SR₁ or C(O)R₂;

[0030] R₁ is hydrogen, or C₁-C₆ alkyl which may be substituted by one ortwo substituents R₆ independently selected from the group consisting ofhydroxy, fluoro, chloro, bromo, iodo, C₁-C₆ alkoxy, O—C(O)—(C₁-C₆alkyl), O—C(O)—N(C₁-C₄ alkyl)(C₁-C₂ alkyl); amino, NH(C₁-C₄ alkyl),S(C₁-C₆ alkyl), OC(O)NH(C₁-C₄alkyl), N(C₁-C₂ alkyl)C(O)(C₁-C₄ alkyl),NHC(O)(C₁-C₄ alkyl), COOH, CO(C₁-C₄ alkyl), C(O)NH(C₁-C₄ alkyl),C(O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SH, CN, NO₂, SO(C₁-C₄ alkyl); SO₂(C₁-C₄alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), and saidC₁-C₆ alkyl may have one or two double or triple bonds;

[0031] R₂ is C₁-C₁₂ alkyl, aryl or (C₁-C₁₀ alkylene)aryl wherein saidaryl is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinolyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl,benzothiazolyl, isothiazolyl, benzisothiazolyl, thiazolyl, isoxazolyl,benzisoxazolyl, benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl,azaindolyl, oxazolyl, or benzoxazolyl; 3- to 8-membered cycloalkyl or(C₁-C₆ alkylene) cycloalkyl, wherein said cycloalkyl may have one or twoof O, S or N—Z, wherein Z is hydrogen, substituted , independently, forone or two carbons of said cycloalkyl, C₁-C₄ alkyl, benzyl or C₁-C₄alkanoyl, wherein R² may be substituted independently by from one tothree of chloro, fluoro, or C₁-C₄ alkyl, or one of hydroxy, bromo, iodo,C₁-C₆ alkoxy, OC(O)(C₁-C₆ alkyl), O—C—N(C₁-C₄ alkyl)(C₁-C₂ alkyl),S(C₁-C₆ alkyl), NH₂, NH(C₁-C₂ alkyl), N(C₁-C₄ alkyl) C(O)(C₁-C₄ alkyl),NHC(O)(C₁-C₄ alkyl), COOH, C(O)O(C₁-C₄ alkyl), C(O)NH(C₁-C₄ alkyl),C(O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SH, CN, NO₂, SO(C₁-C₄ alkyl), SO₂(C₁-C₄alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), and whereinsaid C₁-C₁₂ alkyl or C₁-C₁₀ alkylene may have one to three double ortriple bonds; or

[0032] NR₁R₂ or CR₁R₂R₁₁ may form a 4- to 8-membered ring optionallyhaving one or two double bonds or one or two of O, S or N—Z wherein Z ishydrogen, C₁-C₄ alkyl, benzyl, or C₁-C₄ alkanoyl;

[0033] R₃ is hydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo,hydroxy, amino, O(C₁-C₆ alkyl), NH(C₁-C₆ alkyl), N(C₁-C₄ alkyl)(C₁-C₂alkyl), SH, S(C₁-C₄ alkyl), SO(C₁-C₄ alkyl), or SO₂(C₁-C₄ alkyl),wherein said C₁-C₄ alkyl and C₁-C₆ alkyl may have one or two double ortriple bonds and may be substituted by from 1 to 3 R₇ substituentsindependently selected from the group consisting of hydroxy, amino,C₁-C₃ alkoxy, dimethylamino, diethylamino, methylamino, ethylamino,NHC(O)CH₃, fluoro, chloro or C₁-C₃ thioalkyl;

[0034] R₄ is hydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo, C₁-C₆alkoxy, amino, NH(C₁-C₆ alkyl), N(C₁-C₆ alkyl) (C₁-C₂ alkyl),SO_(n)(C₁-C₆ alkyl), wherein n is 0, 1 or 2, cyano, hydroxy, carboxy, oramido, wherein said C₁-C₆ alkyls may be substituted by one to three ofhydroxy, amino, carboxy, amido, NHC(O)(C₁-C₄ alkyl), NH(C₁-C₄ alkyl),N(C₁-C₄ alkyl)(C₁-C₂ alkyl), C(O)O(C₁-C₄ alkyl), C₁-C₃ alkoxy, C₁-C₃thioalkyl, fluoro, bromo, chloro, iodo, cyano or nitro;

[0035] R₅ is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinolyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl,benzothiazolyl, isothiazolyl, benzoisothiazolyl, thiazolyl, isoxazolyl,benzisoxazolyl, benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl,pyrrolopyridyl benzoxazolyl, oxazolyl, pyrrolidinyl, thiazolidinyl,piperazinyl, piperidinyl, or tetrazolyl, wherein each one of the abovegroups may be substituted independently by from one to three of fluoro,chloro, bromo, formyl, C₁-C₆ alkyl, C₁-C₆ alkoxy or trifluoromethyl, orone of hydroxy, iodo, cyano, nitro, amino, cyclopropyl, NH(C₁-C₄ alkyl),N(C₁-C₄ alkyl)(C₁-C₂ alkyl), COO(C₁-C₄ alkyl), CO(C₁-C₄ alkyl),SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SO₂NH₂, NHSO₂(C₁-C₄alkyl), S(C₁-C₆ alkyl), SO₂(C₁-C₆ alkyl), wherein said C₁-C₄ alkyl andC₁-C₆ alkyl may have one double or triple bond and may be substituted byone or two of fluoro, chloro, hydroxy, amino, methylamino, dimethylaminoor acetyl; with the proviso that R₅ is not unsubstituted phenyl;

[0036] R₁₁ is hydrogen, hydroxy, fluoro, chloro, COO(C₁-C₂ alkyl),cyano, or CO(C₁-C₂ alkyl); and

[0037] R₁₂ is hydrogen or C₁-C₄ alkyl;

[0038] (a) A is not straight chain C₁-C₁₂ alkyl;

[0039] (b) when R₃ is hydrogen, A is benzyl or phenethyl, and R₄ isfluoro, chloro, bromo or iodo, then R₅ is not 5′-deoxy-ribofuranosyl or5′-amino-5′-deoxy-ribofuranosyl; and

[0040] (c) when R⁵ is phenyl, said phenyl is substituted by two or threesubstituents.

[0041] II. The invention also relates to use of a CRF antagonist of thefollowing formula, described in WO 94/13676:

[0042] and the pharmaceutically acceptable acid addition salts thereof,wherein

[0043] B is NR₁R₂, CR₁R₂R₁₁, C(═CR₂R₁₂)R₁, NHR₁R₂R₁₁, OCR₁R₂R₁₁,SCR₁R₂R₁₁, NHNR₁R₂, CR₂R₁₁NHR₁, CR₂R₁₁OR₁, CR₂R₁₁SR₁, or C(O)R₂;

[0044] R₁ is hydrogen, or C₁-C₆ alkyl which may be substituted by one ortwo substituents R₇ independently selected from the group consisting ofhydroxy, fluoro, chloro, bromo, iodo, C₁-C₈ alkoxy, O—C(═O)—(C₁-C₆alkyl), O—C(═O)NH(C₁-C₄ alkyl), O—C(═O)—N(C₁-C₄ alkyl)(C₁-C₂ alkyl),amino, NH(C₁-C₄ alkyl), N(C₁-C₂ alkyl)(C₁-C₄ alkyl), S(C₁-C₆ alkyl),N(C₁-C₄alkyl)C(═O)(C₁-C₄ alkyl), NH(C₁-C₄ alkyl), COOH, C(═O)O(C₁-C₄alkyl), C(═O)NH(C₁-C₄ alkyl), C(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SH, CN,NO₂, SO(C₁-C₄ alkyl), SO₂(C₁-C₄ alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl), and said C₁-C₆ alkyl may contain one or two doubleor triple bonds;

[0045] R₂ is C₁-C₁₂ alkyl, aryl or (C₁-C₁₀ alkylene)aryl wherein saidaryl is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, benzisothiazolyl, thiazolyl, isoxazolyl, benzisoxazolyl,benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridyl,oxazolyl, or benzoxazolyl; 3- to 8-membered cycloalkyl or (C₁-C₆alkylene) cycloalkyl, wherein said cycloalkyl may contain one or two ofO, S or N—Z wherein Z is hydrogen, C₁-C₄ alkyl, benzyl or C₁-C₄alkanoyl, wherein R₂ may be substituted independently by from one tothree of chloro, fluoro, or C₁-C₄ alkyl, or one of hydroxy, bromo, iodo,C₁-C₆ alkoxy, O—C(═O)—(C₁-C₆ alkyl), O—C—N(C₁-C₄ alkyl)(C₁-C₂ alkyl),S(C₁-C₆ alkyl), NH₂, NH(C₁-C₂ alkyl), N(C₁-C₂ alkyl) (C₁-C₄ alkyl),N(C₁-C₄)—C(═O)(C₁-C₄ alkyl), NHC(═O)(C₁-C₄), COOH, C(═O)O(C₁-C₄ alkyl),C(═O)NH(C₁-C₄ alkyl), C(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SH, CN, NO₂,SO(C₁-C₄ alkyl), SO₂(C₁-C₄ alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl), and wherein said C₁-C₁₂ alkyl or C₁-C₁₀ alkylenemay contain one to three double or triple bonds; or

[0046] NR₁R₂ or CR₁R₂R₁₁ may form a saturated 3- to 8 memberedcarbocyclic ring of which the 5- to 8-membered ring contain one or twodouble bonds or one or two of O, S or N—Z wherein Z is hydrogen, C₁-C₄alkyl, benzyl or C₁-C₄ alkanoyl;

[0047] R₃ is hydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo,hydroxy, amino, O(C₁-C₆ alkyl), NH(C₁-C₆ alkyl), N(C₁-C₄ alkyl)(C₁-C₂alkyl), SH, S(C₁-C₄ alkyl), SO(C₁-C₄ alkyl), or SO₂(C₁-C₄ alkyl),wherein said C₁-C₄ alkyl and C₁-C₆ alkyl may contain from one or twodouble or triple bonds and may be substituted by from 1 to 3substituents R₈ independently selected from the group consisting ofhydroxy, amino, C₁-C₃ alkoxy, dimethylamino, diethylamino, methylamino,ethylamino, NHCH₃, fluoro, chloro or C₁-C₃ thioalkyl;

[0048] R₄ and R₆ are each independently hydrogen, C₁-C₆ alkyl, fluoro,chloro, bromo, iodo, C₁-C₆ alkoxy, amino, NH(C₁-C₆ alkyl), N(C₁-C₆alkyl)(C₁-C₂ alkyl), SO_(n)(C₁-C₆ alkyl), wherein n is 0, 1 or 2, cyano,hydroxy, carboxy, or amido, wherein said C₁-C₆ alkyls may be substitutedby one to three of hydroxy, amino, carboxy, amido, NHC(═O)(C₁-C₄ alkyl),NH(C₁-C₄ alkyl), N(C₁-C₄ alkyl)(C₁-C₂ alkyl), C(═O)O(C₁-C₄ alkyl), C₁-C₃alkoxy, C₁-C₃ thioalkyl, fluoro, bromo, chloro, iodo, cyano or nitro;

[0049] R₅ is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, benzisothiazolyl, thiazolyl, isoxazolyl, benzisoxazolyl,benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl, azaindolyl,benzoxazolyl, oxazolyl, pyrrolidinyl, thiazolidinyl, morpholinyl,piperidinyl, piperazinyl, tetrazolyl, or 3- to 8-membered cycloalkyl or9- to 12-membered bicycloalkyl, optionally containing one to three of O,S or N—Z wherein Z is hydrogen, C₁-C₄ alkyl, C₁-C₄ alkanoyl, phenyl orphenylmethyl, wherein each one of the above groups may be substitutedindependently by from one to four of fluoro, chloro, C₁-C₆ alkyl, C₁-C₆alkoxy or trifluoromethyl, or one of bromo, iodo, cyano, nitro, amino,NH(C₁-C₄ alkyl), N(C₁-C₄)(C₁-C₂ alkyl), COO(C₁-C₄ alkyl), CO(C₁-C₄alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SO₂NH₂,NHSO₂(C₁-C₄ alkyl), S(C₁-C₆ alkyl), SO₂(C₁-C₆ alkyl), wherein said C₁-C₄alkyl and C₁-C₆ alkyl may be substituted by one or two of fluoro,chloro, hydroxy, amino, methylamino, dimethylamino or acetyl; with theproviso that R₅ is not unsubstituted phenyl;

[0050] R₁₁ is hydrogen, hydroxy, fluoro, chloro, COO(C₁-C₂ alkyl),cyano, or CO(C₁-C₂ alkyl); and

[0051] R₁₂ is hydrogen or C₁-C₄ alkyl; with the proviso that (1) when R₅is 4-bromophenyl, R₃ is hydrogen, and R₄ and R₆ are methyl, then B isnot methylamino

[0052] ethyl, and (2) when R₅ is 4-bromophenyl, and R₃, R₄ and R₆ aremethyl, then B is not 2-hydroxyethylamino.

[0053] III. It is also possible to employ a CRF antagonist that has astructure selected from the group shown below, and pharmaceuticallyacceptable salts and esters thereof, as described in WO 95/33750:

[0054] or a pharmaceutically acceptable salt thereof, wherein

[0055] the dashed lines represent optional double bonds;

[0056] A is CR₇or N;

[0057] B is NR₁R₂, CR₁R₂R₁₁, C(═CR₂R₁₂)R₁, NHCHR₁R₂, OCHR₁R₂, SCHR₁R₂,CHR₂OR₁₂, CHR₂SR₁₂, C(S)R₂ or C(O)R₂;

[0058] G is oxygen, sulfur, NH, NH₃, hydrogen, methoxy, ethoxy,trifluoromethoxy, methyl, ethyl, thiomethoxy, NH₂, NHCH₃, N(CH₃)₂ ortrifluromethyl;

[0059] Y is CH or N;

[0060] Z is NH, O, S, N (C₁-C₂ alkyl), or CR₁₃R₁₄, wherein R₁₃ and R₁₄are each independently hydrogen, trifluoromethyl, or C₁-C₄ alkyl, or oneof R₁₃ and R₁₄ may be cyano, chloro, bromo, iodo, fluoro, hydroxy,O(C₁-C₂ alkyl), amino, NH(C₁-C₂ alkyl), or CR₁₃R₁₄ may be C═O orcyclopropyl;

[0061] R₁ is C₁-C₆ alkyl which may be substituted by one or twosubstituents R₈ independently selected from the group consisting ofhydroxy, fluoro, chloro, bromo, iodo, C₁-C₄ alkoxy, O—CO—(C₁-C₄ alkyl),O—CO—NH(C₁-C₄ alkyl), O—CO—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), NH(C₁-C₄ alkyl),N(C₁-C₂ alkyl)(C₁-C₄ alkyl), S(C₁-C₄ alkyl), N(C₁-C₄alkyl)CO(C₁-C₄alkyl), NHCO(C₁-C₄ alkyl), COO(C₁-C₄ alkyl), CONH(C₁-C₄ alkyl),CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), S(C₁-C₄ alkyl), CN, NO₂, SO(C₁-C₄ alkyl),SO₂(C₁-C₄ alkyl), and said C₁-C₆ alkyl or C₁-C₄ alkyl may contain onedouble or triple bond;

[0062] R₂ is C₁-C₁₂ alkyl, aryl or (C₁-C₄ alkylene)aryl wherein saidaryl is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, indolyl,or benzoxazolyl; 3- to 8-membered cycloalkyl or (C₁-C₆alkylene)cycloalkyl, wherein said cycloalkyl may contain one or two ofO, S or N—R₉ wherein R₉ is hydrogen, or C₁-C₄ alkyl, wherein the abovedefined R₂ may be substituted independently by from one to three ofchloro, fluoro, or C₁-C₄ alkyl, or one of bromo, iodo, C₁-C₆ alkoxy,O—CO—(C₁-C₆ alkyl), O—CO—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), S(C₁-C₆ alkyl),CN, NO₂, SO(C₁-C₄ alkyl), or SO₂(C₁-C₄ alkyl), and wherein said C₁-C₁₂alkyl or C₁-C₄ alkylene may contain one double or triple bond; or

[0063] NR₁R₂ or CR₁R₂R₁₁ may form a saturated 5- to 8-memberedcarbocyclic ring which may contain one or two double bonds or one or twoof O or S;

[0064] R₃ is methyl, ethyl, fluoro, chloro, bromo, iodo, cyano, methoxy,OCF₃, methylthio, methylsulfonyl, CH₂OH or CH₂OCH₃;

[0065] R₄ is hydrogen, C₁-C₄ alkyl, fluoro, chloro, bromo, iodo, C₁-C₄alkoxy, amino, nitro, NH(C₁-C₄ alkyl), N(C₁-C₄ alkyl)(C₁-C₂ alkyl),SO_(n)(C₁-C₄ alkyl), wherein n is 0, 1 or 2, cyano, hydroxy, CO(C₁-C₄alkyl), CHO, or COO(C₁-C₄ alkyl), wherein said C₁-C₄ alkyl may containone or two double or triple bonds and may be substituted by one or twoof hydroxy, amino, carboxy, NHCOCH₃, NH(C₁-C₂ alkyl), N(C₁-C₂ alkyl)₂,COO(C₁-C₄ alkyl), CO(C₁-C₄ alkyl), C₁-C₃ alkoxy, C₁-C₃ thioalkyl,fluoro, chloro, cyano or nitro;

[0066] R₅ is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, pyrimidyl, furanyl, benzofuranyl, benzothiazolyl, or indolyl,wherein each one of the above groups R₅ is substituted independently byfrom one to three of fluoro, chloro, C₁-C₆ alkyl, or C₁-C₆ alkoxy, orone of hydroxy, iodo, bromo, formyl, cyano, nitro, trifluoromethyl,amino, NH(C₁-C₄ alkyl), N(C₁-C₆)(C₁-C₂ alkyl), COOH, COO(C₁-C₄ alkyl),CO(C₁-C₄ alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl),SO₂NH₂, NHSO₂(C₁-C₄ alkyl), S(C₁-C₆ alkyl), or SO₂(C₁-C₆ alkyl), whereinsaid C₁-C₄ alkyl and C₁-C₆ alkyl may be substituted by one or two offluoro, hydroxy, amino, methylamino, dimethylamino or acetyl;

[0067] R₆ is hydrogen, or C₁-C₆ alkyl, wherein said C₁-C₆ alkyl may besubstituted by one hydroxy, methoxy, ethoxy or fluoro;

[0068] R₇ is hydrogen, C₁-C₄ alkyl, fluoro, chloro, bromo, iodo, cyano,hydroxy, O(C₁-C₄ alkyl), C(O)(C₁-C₄ alkyl), or C(O)O(C₁-C₄ alkyl),wherein the C₁-C₄ alkyl groups may be substituted with one hydroxy,chloro or bromo, or one to three fluoro;

[0069] R₁₁ is hydrogen, hydroxy, fluoro, or methoxy;

[0070] R₁₂ is hydrogen or C₁-C₄ alkyl; and

[0071] R₁₆ and R₁₇ are each independently hydrogen, hydroxy, methyl,ethyl, methoxy, or ethoxy, except that they are not both methoxy orethoxy, and CR₄R₆ and CR₁₆R₁₇ each independently may be C═O.

[0072] IV. It also possible to employ a CRF antagonist of the followingformula, disclosed in WO 95/34563:

[0073] and the pharmaceutically acceptable acid addition salts thereof,wherein

[0074] A is N or —CR₆;

[0075] B is —NR₁R₂, —CR₁R₂R₁₁, —C(═CR₂R₁₂)R₁, —NHCHR₁R₂, —OCHR₁R₂,—SCHR₁R₂, —CHR₂OR₁₂, —CHR₂SR₁₂, —C(S)R₁, or —C(O)R₁;

[0076] R₁ is C₁-C₆ alkyl which may optionally be substituted with one ortwo substituents independently selected from the group consisting ofhydroxy, fluoro, chloro, bromo, iodo, C₁-C₄ alkoxy, —O—CO—(C₁-C₄ alkyl),—O—CO—NH(C₁-C₄ alkyl), —O—CO—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —NH(C₁-C₄alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —S(C₁-C₄ alkyl),—N(C₁-C₄alkyl)CO(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COO(C₁-C₄ alkyl),—CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), CN, NO₂, —SO(C₁-C₄alkyl), —SO₂(C₁-C₄ alkyl), and wherein any of the foregoing C₁-C₄ alkyland C₁-C₆ alkyl groups may optionally contain one carbon-carbon doubleor triple bond;

[0077] R₂ is C₁-C₁₂ alkyl, aryl, —(C₁-C₄ alkylene)aryl wherein said arylis phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, benzisothiazolyl, thiazolyl, isoxazolyl, benzisoxazolyl,benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl, oxazolyl, orbenzoxazolyl; or 3- to 8-membered cycloalkyl or —(C₁-C₆alkylene)cycloalkyl, wherein one or two of the ring carbons of saidcycloalkyl having at least 4 ring members and the cycloalkyl moiety ofsaid —(C₁-C₆ alkylene)cycloalkyl having at least 4 ring members mayoptionally be replaced by an oxygen or sulfur atom or by N—Z wherein Zis hydrogen; or C₁-C₄ alkyl, and wherein each of said groups R₂ mayoptionally be substituted with from one to three substituentsindependently selected from chloro, fluoro, and C₁-C₄ alkyl, or by onesubstituent selected from bromo, iodo, C₁-C₆ alkoxy, —O—CO—(C₁-C₆alkyl), —S(C₁-C₆ alkyl), —COO(C₁-C₄ alkyl), CN, NO₂, —SO(C₁-C₄ alkyl),and —SO₂(C₁-C₄ alkyl), and wherein said C₁-C₁₂ alkyl and the C₁-C₄alkylene moiety of said —(C₁-C₄ alkylene)aryl may optionally contain onecarbon-carbon double or triple bond;

[0078] or —NR₁R₂ may form a saturated 5- to 8-membered heterocyclicring, or —CHR₁R₂ may form a saturated 5- to 8-membered carbocyclic ring,wherein each of these rings may optionally contain one or twocarbon-carbon double bonds and wherein one or two of the carbon atoms ofeach of these rings may optionally be replaced with a sulfur or oxygenatom;

[0079] R₃ is C₁-C₄ alkyl, fluoro, chloro, bromo, iodo, —CH₂OH, —CH₂OCH₃,—O(C₁-C₃ alkyl), —S(C₁-C₃ alkyl), or —SO₂(C₁-C₃ alkyl), wherein saidC₁-C₃ alkyl may optionally contain one carbon-carbon double or triplebond;

[0080] R₄ is hydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo, C₁-C₄alkoxy, amino, —NHCH₃, —N(CH₃)₂, —CH₂OH, —CH₂OCH₃, or —SO_(n)(C₁-C₄alkyl), wherein n is 0, 1 or 2, cyano, hydroxy, —CO(C₁-C₄ alkyl), —CHO,or —COO(C₁-C₄ alkyl) wherein the C₁-C₄ alkyl moieties in the foregoingR₄ groups may optionally contain one carbon-carbon double or triplebond;

[0081] R₅ is phenyl, naphthyl, thienyl, benzothienyl, pyridyl,pyrimidyl, benzofuranyl, pyrazinyl or benzothiazolyl, wherein each oneof said groups R₅ may optionally be substituted with from one to threesubstituents independently selected from fluoro, chloro, C₁-C₆ alkyl andC₁-C₆ alkoxy, or by one substituent selected from iodo, hydroxy, bromo,formyl, cyano, nitro, amino, trifluoromethyl, —NH(C₁-C₄ alkyl),—N(C₁-C₆)(C₁-C₂ alkyl), —COO(C₁-C₄ alkyl), —CO(C₁-C₄ alkyl), —COOH,—SO₂NH(C₁-C₄ alkyl), —SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —SO₂NH₂,—NHSO₂(C₁-C₄ alkyl), —S(C₁-C₆ alkyl) and —SO₂(C₁-C₆ alkyl), wherein eachof said C₁-C₄ alkyl and C₁-C₆ alkyl moieties in the foregoing R⁵ groupsmay optionally be substituted with one to three fluorine atoms;

[0082] R₆ is hydrogen, C₁-C₄ alkyl, fluoro, chloro, bromo, iodo, —CH₂OH,—CH₂OCH₃, or C₁-C₄ alkoxy;

[0083] R₇ is hydrogen, C₁-C₄ alkyl, fluoro, chloro, bromo, iodo,—O(C₁-C₄ alkyl), cyano, —CH₂OH, —CH₂O(C₁-C₂ alkyl), —CO(C₁-C₂ alkyl), or—COO(C₁-C₂ alkyl);

[0084] R₁₁ is hydrogen, hydroxy, fluoro, or methoxy; and

[0085] R₁₂ is hydrogen or C₁-C₄ alkyl;

[0086] with the proviso that when A is N, then: (a) B is notunsubstituted alkyl; (b) R₅ is not unsubstituted phenyl ormonosubstituted phenyl; and (c) R₃ is not unsubstituted alkyl;

[0087] or a pharmaceutically acceptable salt of such compound.

[0088] V. In another embodiment, the CRF antagonist is of the followingformula, disclosed in EP 778277:

[0089] or a pharmaceutically acceptable salt thereof, wherein

[0090] the dashed lines represent optional double bonds;

[0091] A is nitrogen or CR⁷;

[0092] B is —NR¹R², —CR¹R²R¹⁰, —C(═CR²R¹¹)R¹, —NHCR¹R²R¹⁰, —OCR¹R²R¹⁰,—SCR¹R²R¹⁰, —CR²R¹⁰NHR¹, —CR²R¹⁰OR¹, —CR²R¹⁰SR¹ or —COR²;

[0093] D is nitrogen and is single bonded to all atoms to which it isattached, or D is carbon and is either double bonded to E in formulas Iand II or double bonded to the adjacent carbon atom common to both fusedrings in formula III, or D is CH and is single bonded to E in formulas Iand II;

[0094] E is nitrogen, CH or carbon;

[0095] F is oxygen, sulfur, CHR⁴ or NR⁴ when it is single bonded to Eand F is nitrogen or CR⁴ when it is double bonded to E;

[0096] G, when single bonded to E, is hydrogen, C₁-C₄ alkyl, —S(C₁-C₄alkyl), —O(C₁-C₄ alkyl), NH₂, —NH(C₁-C₄ alkyl) or —N(C₁-C₂ alkyl)(C₁-C₄alkyl), wherein each of the C₁-C₄ alkyl groups of G may optionally besubstituted with one hydroxy, —O(C₁-C₂ alkyl) or fluoro group; G, whendouble bonded to E, is oxygen, sulfur or NH; and G, when E is nitrogenand double bonded to D or F, is absent;

[0097] R¹ is hydrogen, C₁-C₆ alkyl optionally substituted with one ortwo substituents R⁸ independently selected from hydroxy, fluoro, chloro,bromo, iodo, C₁-C₄ alkoxy, CF₃, —C(═O)O—(C₁-C₄)alkyl, —OC(═O)(C₁-C₄alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —NHCO(C₁-C₄ alkyl), —COOH,—COO(C₁-C₄ alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl),—S(C₁-C₄ alkyl), —CN, —NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl),—SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), wherein each ofthe C₁-C₄ alkyl groups in the foregoing R¹ groups may optionally containone or two double or triple bonds;

[0098] R² is C₁-C₁₂ alkyl which may optionally contain from one to threedouble or triple bonds, aryl or (C₁-C₄ alkylene)aryl, wherein said aryland the aryl moiety of said (C₁-C₄ alkylene)aryl is selected fromphenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl,pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridyl, oxazolyl andbenzoxazolyl; C₃-C₈ cycloalkyl or (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl),wherein one or two of the carbon atoms of said cycloalkyl and the 5 to 8membered cycloalkyl moieties of said (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl)may optionally and independently be replaced by an oxygen or sulfur atomor by NZ² wherein Z² is selected from hydrogen, C₁-C₄ alkyl, benzyl andC₁-C₄ alkanoyl, and wherein each of the foregoing R² groups mayoptionally be substituted with from one to three substituentsindependently selected from chloro, fluoro, hydroxy and C₁-C₄ alkyl, orwith one substituent selected from bromo, iodo, C₁-C₆ alkoxy,—OC(═O)(C₁-C₆ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₆alkyl), amino, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —N(C₁-C₄alkyl)—CO—(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄ alkyl),—CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —SH, —CN, —NO₂,—SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl);

[0099] —NR¹R² or CR¹R²R¹⁰ may form a saturated 3 to 8 memberedcarbocyclic ring which may optionally contain from one to three doublebonds and wherein one or two of the ring carbon atoms of such 5 to 8membered rings may optionally and independently be replaced by an oxygenor sulfur atom or by NZ³ wherein Z³ is hydrogen, C₁-C₄ alkyl, benzyl orC₁-C₄ alkanoyl;

[0100] R³ is hydrogen, C₁-C₄ alkyl, —O(C₁-C₄ alkyl), chloro, fluoro,bromo, iodo, —CN, —S(C₁-C₄ alkyl) or —SO₂(C₁-C₄ alkyl) wherein each ofthe (C₁-C₄ alkyl) moieties in the foregoing R³ groups may optionally besubstituted with one substituent R⁹ selected from hydroxy, fluoro and(C₁-C₂ alkoxy);

[0101] each R⁴ is, independently, hydrogen, (C₁-C₆ alkyl), fluoro,chloro, bromo, iodo, hydroxy, cyano, amino, nitro, —O(C₁-C₄ alkyl),—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₄ alkyl), —SO(C₁-C₄ alkyl),—SO₂(C₁-C₄)alkyl, —CO(C₁-C₄ alkyl), —C(═O)H or —C(═O)O(C₁-C₄alkyl),wherein each of the (C₁-C₆ alkyl) and (C₁-C₄ alkyl) moieties in theforegoing R⁴ groups may optionally contain one or two double or triplebonds and may optionally be substituted with one or two substituentsindependently selected from hydroxy, amino, C₁-C₃ alkoxy, dimethylamino,methylamino, ethylamino, —NHC(═O)CH₃, fluoro, chloro, C₁-C₃ thioalkyl,—CN, —COOH, —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄ alkyl) and —NO₂;

[0102] R⁵ is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, furanyl, benzofuranyl, benzothiazolyl, benzisothiazolyl,benzisoxazolyl, benzimidazolyl, indolyl, benzoxazolyl or C₃-C₈cycloalkyl wherein one or two of the carbon atoms of said cycloalkylrings that contain at least 5 ring members may optionally andindependently be replaced by an oxygen or sulfur atom or by NZ⁴ whereinZ⁴ is hydrogen, C₁-C₄ alkyl or benzyl; and wherein each of the foregoingR⁵ groups is substituted with from one to four substituents R¹² whereinone to three of said substituents may be selected, independently, fromchloro, C₁-C₆ alkyl and —O(C₁-C₆ alkyl) and one of said substituents maybe selected from bromo, iodo, formyl, —CN, —CF₃, —NO₂, —NH₂, —NH(C₁-C₄alkyl), —N(C₁-C₂ alkyl)(C₁-C₆ alkyl), —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄alkyl), —COOH, —SO₂NH(C₁-C₄ alkyl), —SO₂N(C₁-C₂ alkyl)(C₁-C₄ alkyl),—SO₂NH₂, —NHSO₂(C₁-C₄ alkyl), —S(C₁-C₆ alkyl) and —SO₂(C₁-C₆ alkyl), andwherein each of the C₁-C₄ alkyl and C₁-C₆ alkyl moieties in theforegoing R⁵ groups may optionally be substituted with one or twosubstituents independently selected from fluoro, hydroxy, amino,methylamino, dimethylamino and acetyl;

[0103] R⁷ is hydrogen, C₁-C₄ alkyl, halo, cyano, hydroxy, —O(C₁-C₄alkyl) —C(═O)(C₁-C₄ alkyl), —C(═O)O(C₁-C₄alkyl), —OCF₃, —CF₃, —CH₂OH,—CH₂O(C₁-C₄ alkyl);

[0104] R¹⁰ is hydrogen, hydroxy, methoxy or fluoro;

[0105] R¹¹ is hydrogen or C₁-C₄ alkyl; and

[0106] Z is NH, oxygen, sulfur, —N(C₁-C₄ alkyl), —NC(═O)(C₁-C₂ alkyl),NC(═O)O(C₁-C₂alkyl) or CR¹³R¹⁴ wherein R¹³ and R¹⁴ are independentlyselected from hydrogen, trifluoromethyl and methyl with the exceptionthat one of R¹³ and R¹⁴ can be cyano;

[0107] with the proviso that: (a) in the five membered rings ofstructures I, II and Ill, there can not be two double bonds adjacent toeach other; and (b) when R⁴ is attached to nitrogen, it is not halo,cyano or nitro;

[0108] or a pharmaceutically acceptable salt of such compound.

[0109] VI. The CRF antagonist can also be of the following formula,disclosed in WO 98/05661:

[0110] wherein the dashed lines represent optional double bonds;

[0111] A is nitrogen or CR⁷;

[0112] B is —NR¹R², —CR¹R²R¹⁰, —C(═CR²R¹¹)R¹, —NHCR¹R²R¹⁰, —OCR¹R²R¹⁰,—SCR¹R²R¹⁰, —CR²R¹⁰NHR¹, —CR²R¹⁰OR¹, —CR²R¹⁰SR¹ or —COR², and is singlebonded to D; or B is —CR¹R², and is double bonded to D and D is carbon;

[0113] D is nitrogen or CR⁴ and is single bonded to all atoms to whichit is attached, or D is carbon and is double bonded to E or doublebonded to B;

[0114] E is oxygen, nitrogen, sulfur, C═O, C═S, CR⁶R¹², NR⁶ or CR⁶; or Eis a two atom spacer, wherein one of the atoms is oxygen, nitrogen,sulfur, C═O, C═S, CR⁶R¹², NR⁶ or CR⁶, and the other is CR⁶R¹² or CR⁹;

[0115] K and G are each, independently, C═O, C═S, sulfur, oxygen, CHR⁸or NR⁸ when single bonded to both adjacent ring atoms, or nitrogen orCR⁸ when it is double bonded to an adjacent ring atom;

[0116] the 6- or 7-membered ring that contains D, E, K and G may containfrom one to three double bonds, from zero to two heteroatoms selectedfrom oxygen, nitrogen and sulfur, and from zero to two C═O or C═Sgroups, wherein the carbon atoms of such groups are part of the ring andthe oxygen and sulfur atoms are substituents on the ring;

[0117] R¹ is C₁-C₆ alkyl optionally substituted with from one or twosubstituents independently selected from hydroxy, fluoro, chloro, bromo,iodo, C₁-C₄ alkoxy, CF₃, —C(═O)(C₁-C₄alkyl), —C(═O)—O—(C₁-C₄)alkyl,—OC(═O)(C₁-C₄ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —NHCO(C₁-C₄alkyl), —COOH, —COO(C₁-C₄ alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄alkyl)(C₁-C₂ alkyl), —S(C₁-C₄ alkyl), —CN, —NO₂, —SO(C₁-C₄ alkyl),—SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄ alkyl)(C₁-C₂alkyl), wherein each of the C₁-C₄ alkyl groups in the foregoing R¹groups may optionally contain one or two double or triple bonds;

[0118] R² is C₁-C₁₂ alkyl which may optionally contain from one to threedouble or triple bonds, aryl or (C₁-C₄ alkylene)aryl, wherein said aryland the aryl moiety of said (C₁-C₄ alkylene)aryl is selected fromphenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl,pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridyl, oxazolyl andbenzoxazolyl; C₃-C₈ cycloalkyl or (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl),wherein one or two of the carbon atoms of said cycloalkyl and the 5 to 8membered cycloalkyl moieties of said (C₁-C₆ alkylene)(C₃-C₈ cycloalkylmay optionally and independently be replaced by an oxygen or sulfur andwherein each of the foregoing R² groups may optionally be substitutedwith from one to three substituents independently selected from chloro,fluoro, hydroxy and C₁-C₄ alkyl, or with one substituent selected fromC₁-C₆ alkoxy, —OC(═O)(C₁-C₆ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl),—S(C₁-C₆ alkyl), amino, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl),—N(C₁-C₄ alkyl)—CO—(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —SH, —CN,—NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and—SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl);

[0119] —NR¹R² or CR¹R²R¹⁰ may form a ring selected from saturated 3 to 8membered rings, the 5 to 8 membered rings of which may optionallycontain one or two double bonds, and wherein one or two of the ringcarbon atoms of such 5 to 8 membered rings may optionally andindependently be replaced by an oxygen or sulfur atom or by NZ³ whereinZ³ is hydrogen or C₁-C₄ alkyl;

[0120] R³ is hydrogen, C₁-C₄ alkyl, —O(C₁-C₄ alkyl), chloro, fluoro,bromo, iodo, —S(C₁-C₄ alkyl) or —SO₂(C₁-C₄ alkyl);

[0121] R⁴ is hydrogen, C₁-C₂ alkyl, hydroxy or fluoro;

[0122] each R⁶, R⁸ and R⁹ that is attached to a carbon atom is selected,independently, from hydrogen, C₁-C₂ alkyl, fluoro, chloro, bromo, iodo,hydroxy, hydroxymethyl, formyl, trifluoromethyl, cyano, amino, nitro,—O(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₂ alkyl), —S(C₁-C₂ alkyl),—CO(C₁-C₂ alkyl), —C(═O)H or —C(═O)O(C₁-C₂ alkyl), wherein each of theC₁-C₂ alkyl moieties in the foregoing R⁶, R⁸, and R⁹ groups mayoptionally contain one double or triple bond; and each R⁶, R⁸, and R⁹that is attached to a nitrogen atom is selected, independently, fromhydrogen and C₁-C₄ alkyl;

[0123] R⁵ is substituted phenyl, naphthyl, pyridyl or pyrimidyl, whereineach of the foregoing R⁵ groups is substituted with from two to foursubstituents R¹⁵, wherein from one to three of said substituents may beselected, independently, from chloro, C₁-C₆ alkyl, —O(C₁-C₆ alkyl) and—(C₁-C₆alkylene)O(C₁-C₆alkyl), and wherein one of said substituents maybe selected, independently, from bromo, iodo, formyl, cyano,trifluoromethyl, nitro, amino, —NH(C₁-C₄ alkyl), —N(C₁-C₂ alkyl)(C₁-C₆alkyl), —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄ alkyl), —COOH, —SO₂NH(C₁-C₄alkyl), —SO₂N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —SO₂NH₂, —NHSO₂(C₁-C₄ alkyl),—S(C₁-C₆ alkyl) and —SO₂(C₁-C₆ alkyl), and wherein each of the C₁-C₄alkyl and C₁-C₆ alkyl moieties in the foregoing R⁵ groups may optionallybe substituted with one or two substituents independently selected fromfluoro, hydroxy, amino, methylamino, dimethylamino and acetyl;

[0124] R⁷ is hydrogen, methyl, halo (e.q., chloro, fluoro, iodo orbromo), hydroxy, methoxy, —C(═O)(C₁-C₂ alkyl), —C(═O)O(C₁-C₂ alkyl),trifluoromethoxy, hydroxymethyl, trifluoromethyl or formyl;

[0125] R¹⁰ is hydrogen, hydroxy, methoxy or fluoro;

[0126] R¹¹ is hydrogen or C₁-C₄ alkyl;

[0127] R¹² is hydrogen or methyl; and

[0128] Z is NH, oxygen, sulfur, —N(C₁-C₄ alkyl), or CR¹³R¹⁴ wherein R¹³and R¹⁴ are independently selected from hydrogen, and methyl with theexception that one of R¹³ and R¹⁴ may optionally be cyano;

[0129] with the proviso that: (a) in the six or seven membered rings ofstructures in formula I, there can not be two double bonds adjacent toeach other; and (b) when D is carbon and is double bonded to B, then Bis CR¹R²;

[0130] or a pharmaceutically acceptable salt of such compound.

[0131] VII. The CRF antagonist can also be of the following formula,disclosed in WO 98/08847:

[0132] or a pharmaceutically acceptable salt thereof, wherein

[0133] the dashed lines represent optional double bonds;

[0134] A is nitrogen or CR⁷;

[0135] B is —NR¹R², —CR¹R²R¹⁰—C(═CR²R¹¹)R¹, —NHCR¹R²R¹⁰, —OCR¹R²R¹⁰,—SCR¹R²R¹⁰, —CR²R¹⁰NHR¹, —CR²R¹⁰OR¹, —CR²R¹⁰SR¹ or —COR²;

[0136] J and K are each independently nitrogen or carbon and both J andK are not nitrogens;

[0137] D and E are each selected, independently, from nitrogen, CR⁴,C═O, C═S, sulfur, oxygen, CR⁴R⁶ and NR⁸;

[0138] G is nitrogen or carbon;

[0139] the ring containing D, E, G, K, and J in formula I may be asaturated or unsaturated 5-membered ring and may optionally contain oneor two double bonds and may optionally contain from one to threeheteroatoms in the ring and may optionally have one or two C═O or C═Sgroups;

[0140] R¹ is C₁-C₆ alkyl optionally substituted with one or twosubstituents independently selected from hydroxy, fluoro, chloro, bromo,iodo, —O—(C₁-C₄ alkyl), CF₃, —C(═O)O—(C₁-C₄alkyl), —OC(═O)(C₁-C₄ alkyl),—OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —NHCO(C₁-C₄ alkyl), —COOH,—COO(C₁-C₄ alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl),—S(C₁-C₄ alkyl), —CN, —NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl),—SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), wherein each ofthe C₁-C₄ alkyl groups in the foregoing R¹ groups may optionally containone or two double or triple bonds;

[0141] R² is C₁-C₁₂ alkyl which may optionally contain from one to threedouble or triple bonds, aryl or (C₁-C₄ alkylene)aryl, wherein said aryland the aryl moiety of said (C₁-C₄ alkylene)aryl is selected fromphenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl,pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridyl, oxazolyl andbenzoxazolyl; C₃-C₈ cycloalkyl or (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl),wherein one or two of the carbon atoms of said cycloalkyl and the 5 to 8membered cycloalkyl moieties of said (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl)may optionally and independently be replaced by an oxygen or sulfur atomor by NZ² wherein Z² is selected from hydrogen, C₁-C₄ alkyl, benzyl andC₁-C₄ alkanoyl, and wherein each of the foregoing R² groups mayoptionally be substituted with from one to three substituentsindependently selected from chloro, fluoro, hydroxy and C₁-C₄ alkyl, orwith one substituent selected from bromo, iodo, C₁-C₆ alkoxy,—OC(═O)(C₁-C₆ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₆alkyl), amino, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —N(C₁-C₄alkyl)—CO—(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄ alkyl),—CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —SH, —CN, —NO₂,—SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl);

[0142] —NR¹R² or CR¹R²R¹⁰ may form a saturated 3 to 8 memberedcarbocyclic ring which may optionally contain from one to three doublebonds and wherein one or two of the ring carbon atoms of such 5 to 8membered rings may optionally and independently be replaced by an oxygenor sulfur atom or by NZ³ wherein Z³ is hydrogen, C₁-C₄ alkyl, benzyl orC₁-C₄ alkanoyl;

[0143] R³ is hydrogen, C₁-C₄ alkyl, —O(C₁-C₄ alkyl), chloro, fluoro,bromo, iodo, (C₁-C₂ alkylene)—O—(C₁-C₂ alkyl), (C₁-C₂ alkylene)—OH, or—S(C₁-C₄ alkyl);

[0144] each R⁴ is, independently, hydrogen, (C₁-C₆ alkyl), fluoro,chloro, bromo, iodo, hydroxy, cyano, amino, (C₁-C₂ alkylene)—OH, CF₃,CH₂SCH₃, nitro, —O(C₁-C₄ alkyl), —N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₄alkyl), —CO(C₁-C₄ alkyl), —C(═O)H or —C(═O)O(C₁-C₄alkyl);

[0145] R⁶ is hydrogen, methyl or ethyl;

[0146] R⁸ is hydrogen or C₁-C₄ alkyl;

[0147] R⁵ is phenyl, pyridyl, pyrazinyl, pyrimidyl, pyridazinyl andwherein each of the foregoing R⁵ groups is substituted with from one tofour substituents R¹³ wherein one to three of said substituents may beselected, independently, from fluoro, chloro, C₁-C₆ alkyl and —O(C₁-C₆alkyl) and one of said substituents may be selected from bromo, iodo,formyl, OH, (C₁-C₄ alkylene)—OH, (C₁-C₄alkylene)—O—(C₁-C₂ alkyl), —CN,—CF₃, —NO₂, —NH₂, —NH(C₁-C₄ alkyl), —N(C₁-C₂ alkyl)(C₁-C₆ alkyl),—OCO(C₁-C₄ alkyl), (C₁-C₄ alkylene)—O—(C₁-C₄ alkyl), —S(C₁-C₆ alkyl),(C₁-C₄ alkylene)—S—(C₁-C₄ alkyl), —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄alkyl), —COOH, —SO₂NH(C₁-C₄ alkyl), —SO₂N(C₁-C₂ alkyl)(C₁-C₄ alkyl),—SO₂NH₂, —NHSO₂(C₁-C₄ alkyl), —S(C₁-C₆ alkyl) and —SO₂(C₁-C₆ alkyl), andwherein each of the C₁-C₄ alkyl and C₁-C₆ alkyl moieties in theforegoing R⁵ groups may optionally have one or two double bonds;

[0148] R⁷ is hydrogen, C₁-C₄ alkyl, halo (e.g., chloro, fluoro, iodo orbromo), hydroxy, —O(C₁-C₄ alkyl), —C(═O)(C₁-C₄ alkyl), —C(═O)O(C₁-C₄alkyl), —OCF₃, —CF₃, —CH₂OH or —CH₂O(C₁-C₂ alkyl);

[0149] R¹⁰ is hydrogen, hydroxy, methoxy or fluoro;

[0150] R¹¹ is hydrogen or C₁-C₄ alkyl; and

[0151] with the proviso that: a) when both J and K are carbons and D isCR⁴and E is nitrogen, then G can not be nitrogen; (b) when both J and Kare carbons and D and G are nitrogens, then E can not be CR⁴ or C═O orC═S; (c) when both J and K are carbons and D and E are carbons, then Gcan not be nitrogen; (d) when G is carbon, it must be double banded toE; and (e) in the ring containing J, K, D, E and G, there can not be twodouble bonds adjacent to each other;

[0152] and the pharmaceutically acceptable salts of such compounds.

[0153] VII. Other useful CRF antagonists are of the following formula,disclosed in WO 98/08846:

[0154] wherein the dashed lines represent optional double bonds;

[0155] A is nitrogen or CR⁷;

[0156] B is —NR¹R², —CR¹R²R¹⁰, —C(═CR ²R¹¹)R¹, —NHCR¹R²R¹⁰, —OCR¹R²R¹⁰,—SCR¹R²R¹⁰, —CR²R¹⁰NHR¹, —CR²R¹⁰OR¹, —CR²R¹⁰SR¹ or —COR²;

[0157] G is nitrogen or CR⁴ and is single bonded to all atoms to whichit is attached, or G is carbon and is double bonded to K;

[0158] K is nitrogen or CR⁶ when double bonded to G or E, or K isoxygen, sulfur, C═O, C═S, CR⁶R¹²or NR⁸ when single bonded to bothadjacent ring atoms, or K is a two atom spacer, wherein one of the tworing atoms of the spacer is oxygen, nitrogen, sulfur, C═O, C═S, CR⁶R¹²,NR⁶ or CR⁶, and the other is CR⁶R¹² or CR⁹;

[0159] D and E are each, independently, C═O, C═S, sulfur, oxygen, CR⁴R⁶or NR⁸ when single bonded to both adjacent ring atoms, or nitrogen orCR⁴ when it is double bonded to an adjacent ring atom;

[0160] the 6- or 7-membered ring that contains D, E, K and G may containfrom one to three double bonds, from zero to two heteroatoms selectedfrom oxygen, nitrogen and sulfur, and from zero to two C═O or C═Sgroups, wherein the carbon atoms of such groups are part of the ring andthe oxygen and sulfur atoms are substituents on the ring;

[0161] R¹ is C₁-C₆ alkyl optionally substituted with from one or twosubstituents independently selected from hydroxy, fluoro, chloro, bromo,iodo, C₁-C₄ alkoxy, CF₃, —C(═O)(C₁-C₄alkyl), —C(═O)—O—(C₁-C₄)alkyl,—OC(═O)(C₁-C₄ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —NHCO(C₁-C₄alkyl), —COOH, —COO(C₁-C₄ alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄alkyl)(C₁-C₂ alkyl), —S(C₁-C₄ alkyl), —CN, —NO₂, —SO(C₁-C₄ alkyl),—SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄ alkyl)(C₁-C₂alkyl), wherein each of the C₁-C₄ alkyl groups in the foregoing R¹groups may optionally contain one or two double or triple bonds;

[0162] R² is C₁-C₂ alkyl which may optionally contain from one to threedouble or triple bonds, aryl or (C₁-C₄ alkylene)aryl, wherein said aryland the aryl moiety of said (C₁-C₄ alkylene)aryl is selected fromphenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl,pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridyl, oxazolyl andbenzoxazolyl; C₃-C₈ cycloalkyl or (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl),wherein one or two of the carbon atoms of said cycloalkyl and the 5 to 8membered cycloalkyl moieties of said (C₁-C₆ alkylene)(C₃-C₈ cycloalkylmay optionally and independently be replaced by an oxygen or sulfur atomor by NZ wherein Z is hydrogen, C₁-C₄ alkyl or benzyl, and wherein eachof the foregoing R² groups may optionally be substituted with from oneto three substituents independently selected from chloro, fluoro,hydroxy and C₁-C₄ alkyl, or with one substituent selected from C₁-C₆alkoxy, —OC(═O)(C₁-C₆ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl),—S(C₁-C₆ alkyl), amino, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl),—N(C₁-C₄ alkyl)—CO—(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —SH, —CN,—NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and—SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl);

[0163] —NR¹R² or CR¹R²R¹⁰ may form a ring selected from saturated 3 to 8membered rings, the 5 to 8 membered rings of which may optionallycontain one or two double bonds, and wherein one or two of the ringcarbon atoms of such 5 to 8 membered rings may optionally andindependently be replaced by an oxygen or sulfur atom or by NZ² whereinZ² is hydrogen, benzyl or C₁-C₄ alkyl;

[0164] R³ is hydrogen, C₁-C₄ alkyl, —O(C₁-C₄ alkyl), chloro, fluoro,bromo, iodo, —S(C₁-C₄ alkyl) or —SO₂(C₁-C₄ alkyl);

[0165] each R⁸, R⁹ and R¹² is selected, independently, from. hydrogenand C₁-C₂ alkyl;

[0166] each R⁴ and R⁶ that is attached to a carbon atom is selected,independently, from hydrogen and C₁-C₆ alkyl, fluoro, chloro, bromo,iodo, hydroxy, hydroxy (C₁-C₂ alkyl), trifluoromethyl, cyano, amino,nitro, —O(C₁-C₄ alkyl), —N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —CH₂SCH₃, —S(C₁-C₄alkyl), —CO(C₁-C₄ alkyl), —C(═O)H or —C(═O)O(C₁-C₄ alkyl), wherein eachof the C₁-C₂ alkyl moieties in the foregoing R⁴ and R⁶ groups mayoptionally contain one double or triple bond; and R⁶, when attached to anitrogen atom, is selected from hydrogen and C₁-C₄ alkyl;

[0167] R⁵ is substituted phenyl, naphthyl, pyridyl or pyrimidyl, whereineach of the foregoing R⁵ groups is substituted with from two to foursubstituents R¹³, wherein up to three of said substituents may beselected, independently, from chloro, C₁-C₆ alkyl, —O(C₁-C₆ alkyl) and—(C₁-C₆ alkylene)O(C₁-C₆alkyl), and wherein one of said substituents maybe selected, independently, from bromo, iodo, formyl, cyano,trifluoromethyl, nitro, amino, —NH(C₁-C₄ alkyl), —N(C₁-C₂ alkyl)(C₁-C₆alkyl), —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄ alkyl), —COOH, —SO₂NH(C₁-C₄alkyl), —SO₂N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —SO₂NH₂, —NHSO₂(C₁-C₄ alkyl),—(C₀-C₁alkylene)—S—(C₁-C₂alkyl), —(C₀-C₁ alkylene)—SO—(C₁-C₂alkyl),—(C₀-C₁alkylene)—SO₂—(C₁-C₂alkyl) and —(C₁-C₄alkylene)—OH, and whereineach of the C₁-C₄ alkyl and C₁-C₆ alkyl moieties in the foregoing R⁵groups may optionally be substituted with one or two substituentsindependently selected from fluoro, hydroxy, amino, methylamino,dimethylamino and acetyl;

[0168] R⁷ is hydrogen, methyl, halo (e.g., chloro, fluoro, iodo orbromo), hydroxy, methoxy, —C(═O)(C₁-C₂ alkyl), —C(═O)O(C₁-C₂ alkyl),hydroxymethyl, trifluoromethyl or formyl;

[0169] R¹⁰ is hydrogen, hydroxy, methoxy or fluoro; and

[0170] R¹¹ is hydrogen or C₁-C₄ alkyl;

[0171] with the proviso that in the ring containing D, E, K and G offormula I, there can not be two double bonds adjacent to each other;

[0172] and the pharmaceutically acceptable salt of such compound.

[0173] IX. The CRF antagonist may also be of the following formula,disclosed in WO 95/10506:

[0174] or a pharmaceutically, acceptable salt or prodrug thereof,wherein Y is CR^(3a), N, or CR²⁹;

[0175] when Y is CR^(3a) or N:

[0176] R¹ is independently selected at each occurrence from the groupconsisting of C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, halogen, C₁-C₂haloalkyl, NR⁶R⁷, OR⁸, and S(O)_(n)R⁸;

[0177] R³ is C₁-C₄ alkyl, aryl, C₃-C₆ cycloalkyl, C₁-C₂ haloalkyl,halogen, nitro, NR⁶R⁷, OR⁸, S(O)_(n)R⁸ C(═O)R⁹, C(═O)NR⁶R⁷, C(═S)NR⁶R⁷,—(CHR¹⁶)_(k)NR⁶R⁷, (CH₂)_(k)OR⁸, C(═O)NR¹⁰CH(R¹¹)CO₂R¹²,—C(OH)(R²⁵)(R^(25a)), —(CH₂)_(p)S(O)_(n)-alkyl, —(CHR¹⁶)R²⁵,—C(CN)(R²⁵)(R¹⁶) provided that R²⁵ is not —NH— containing rings,—C(═O)R²⁵, —CH(CO₂R¹⁶)₂, NR¹⁰C(═O)CH(R¹¹)NR¹⁰R¹², NR¹⁰CH(R¹¹)CO₂R¹²;substituted C₁-C₄ alkyl, substituted C₂-C₄ alkenyl, substituted C₂-C₄alkynyl, substituted C₁-C₄ alkoxy, aryl-(substituted C₁-C₄) alkyl,aryl-(substituted C₁-C₄) alkoxy, substituted C₃-C₆ cycloalkyl,amino-(substituted C₁-C₄)alkyl, substituted C₁-C₄ alkylamino, wheresubstitution by R²⁷ can occur on any carbon containing substituent;2-pyridinyl, imidazolyl, 3-pyridinyl, 4-pyridinyl, 2-methyl-3-pyridinyl,4-methyl-3-pyridinyl, furanyl, 5-methyl-2-furanyl,2,5-dimethyl-3-furanyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl,2-pheno-thiazinyl, 4-pyrazinyl, azetidinyl, phenyl, 1H-indazolyl,2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl,4-piperidonyl, 4aH-carbazolyl, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl,acridinyl, azocinyl, azepinyl, benzofuranyl, benzothiophenyl,carbazolyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl,furazanyl, imidazolidinyl, indolinyl, indolizinyl, indolyl,isobenzofuranyl, isochromanyl, isoindolinyl, isoindolyl, isoquinolinyl,benzimidazolyl, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl,octahydroisoquinolinyl, oxazolidinyl, oxazolyl, phenanthridinyl,phenanthrolinyl, phenazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl,piperazinyl, piperidinyl, pteridinyl, purinyl, pyranyl, pyrazolidinyl,pyrazolinyl, pyrazolyl, pyridazinyl, pyrimidinyl, pyrrolidinyl,pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl,quinuclidinyl, β-carbolinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl,tetrahydroquinolinyl, tetrazolyl, thianthrenyl, thiazolyl, thiophenyl,triazinyl, xanthenyl; or 1-tetrahydroquinolinyl or2-tetrahydroisoquinolinyl either of which can be substituted with 0-3groups chosen from keto and C₁-C₄ alkyl;

[0178] J, K, and L are independently selected at each occurrence fromthe group of N, CH, and CX′;

[0179] M is CR⁵ or N;

[0180] V is CR^(1a) or N;

[0181] Z is CR² or N;

[0182] R^(1a), R², and R^(3a) are independently selected at eachoccurrence from the group consisting of hydrogen, halo, halomethyl,C₁-C₃ alkyl, and cyano;

[0183] R⁴ is (CH₂)_(m)OR¹⁶, C₁-C₄ alkyl, allyl, propargyl, (CH₂)_(m)R¹³,or —(CH₂)_(m)OC(O)R¹⁶;

[0184] X is halogen, aryl, heteroaryl, S(O)₂R⁸, SR⁸, halomethyl,—(CH₂)_(p)OR⁸, cyano, —(CHR ¹⁶)_(p)NR¹⁴R¹⁵, —C(═O)R⁸, C₁-C₆ alkyl,C₄-C₁₀ cycloalkylalkyl, C₁-C₁₀alkenyl, C₂-C₁₀alkynyl, C₂-C₁₀alkoxy,aryl-(C₂-C₁₀)-alkyl, C₃-C₆cycloalkyl, aryl-(C₁-C₁₀)-alkoxy, nitro,thio-(C₁-C₁₀)-alkyl, —C(═NOR¹⁶)—C₁-C₄—alkyl, —C(═NOR¹⁶)H, or—C(═O)NR¹⁴R¹⁵, where substitution by R¹⁸ can occur on any carboncontaining substituents;

[0185] X′ is independently selected at each occurrence from the groupconsisting of hydrogen, halogen, aryl, heteroaryl, S(O)_(n)R⁸,halomethyl, —(CHR⁶)_(p)OR⁸, cyano, —(CHR¹⁶)_(p)NR¹⁴R¹⁵, C(═O)R⁸, C₁-C₆alkyl, C₂-C₁₀alkenyl, C₂-C₁₀alkynyl, C₁-C₁₀alkoxy, aryl-(C₁-C₁₀)-alkyl,C₃-C₆cycloalkyl, aryl-(C₁-C₁₀)-alkoxy, nitro, thio-(C₁-C₁₀)-alkyl,—C(═NOR¹⁶)—C₁-C₄-alkyl, —C(═NOR¹⁶)H, and —C(═O)NR¹⁴R¹⁵, wheresubstitution by R¹⁶ can occur on any carbon containing substituents;

[0186] R⁵ is halo, —C(═NOR¹⁶)—C₁-C₄-alkyl, C₁-C₄alkyl, C₁-C₃ haloalkyl,—(CHR¹⁶)_(p)OR⁸, —(CHR¹⁶)_(p)S(O)_(n)R⁸, —(CHR⁶)_(p)NR¹⁴R¹⁵, C₃-C₆cycloalkyl, C₂-C₁₀alkenyl, C₂-C₁₀alkynyl, aryl-(C₂-C₁₀)-akyl,aryl-(C₁-C₁₀)-alkoxy, cyano, C₃-C₆ cycloalkoxy, nitro,amino-(C₂-C₁₀)-alkyl, thio-(C₂-C₁₀)-alkyl, SO_(n)(R⁸),C(═O)R⁸—C(═NOR¹⁶)H, or —C(═O)NR¹⁴R¹⁵, where substitution by R¹⁸ canoccur on any carbon containing substituents;

[0187] R⁶ and R⁷ are independently selected at each occurrence from thegroup consisting of hydrogen, C₁-C₆ alkyl, C₃-C₁₀ cycloalkyl, C₁-C₆alkoxy, (C₄-C₁₂)-cycloalkylalkyl, —(CH₂)_(k)R¹³, (CHR¹⁶)_(p)OR⁸,—(C₁-C₆alkyl)-aryl,

[0188] heteroaryl, —S(O)_(z)-aryl or —(C₁-C₆alkyl)-heteroaryl or aryl,wherein the aryl or heteroaryl groups are optionally substituted with1-3 groups selected from the group consisting of hydrogen, halogen,C₁-C₆alkyl, C₁-C₆ alkoxy, amino, NHC(═O)(C₁-C₆ alkyl), NH(C₁-C₆ alkyl),N(C₁-C₆ alkyl)₂, nitro, carboxy, CO₂(C₁-C₆ alkyl), cyano, andS(O)₂—(C₁-C₆-alkyl); or can be taken together to form—(CH₂)_(p)A(CH₂)_(r)—, optionally substituted with 0-3 R¹⁷; or, whenconsidered with the commonly attached nitrogen, can be taken together toform a heterocycle, said heterocycle being substituted on carbon with1-3 groups consisting of hydrogen, C₁-C₆ alkyl, hydroxy, or C₁-C₆alkoxy;

[0189] A is CH₂, O, NR²⁵, C(═O), S(O)_(n), N(C(═O)R¹⁷), N(R¹⁹),C(H)(NR¹⁴R¹⁵), C(H)(OR²⁰), C(H)(C(═O)R²¹), or N(S(O)_(n), R²¹);

[0190] R⁸ is independently selected at each occurrence from the groupconsisting of hydrogen; C₁-C₆ alkyl; -(C₄-C₁₂) cycloalkylalkyl;(CH₂)_(t)R²²; C₃-C₁₀ cycloalkyl; —NR⁶R⁷; aryl; heteroaryl;—NR¹⁶(CH₂)_(n)R⁶R⁷; —(CH₂)_(k)R²⁵; and (CH₂)_(t)heteroaryl or(CH₂)_(t)aryl, either of which can optionally be substituted with 1-3groups selected from the group consisting of hydrogen, halogen, C₁-C₆alkyl, C₁-C₆ alkoxy, amino, NHC(═O)(C₁-C₆ alkyl), NH(C₁-C₆ alkyl),N(C₁-C₆ alkyl)₂, nitro, carboxy, CO₂(C₁-C₆ alkyl), cyano, andS(O)₂(C₁-C₆-alkyl);

[0191] R⁹ is independently selected at each occurrence from R¹⁰,hydroxy, C₁-C₄ alkoxy, C₃-C₆ cycloalkyl, C₂-C₄ alkenyl, aryl substitutedwith 0-3 R¹⁸, and —(C₁-C₆ alkyl)-aryl substituted with 0-3 R¹⁸;

[0192] R¹⁰, R¹⁶, R²³, and R²⁴ are independently selected at eachoccurrence from hydrogen or C₁-C₄ alkyl;

[0193] R¹¹ is C₁-C₄ alkyl substituted with 0-3 groups chosen from thefollowing: keto, amino, sulfhydryl, hydroxyl, guanidinyl,p-hydroxyphenyl, imidazolyl, phenyl, indolyl, and indolinyl, or, whentaken together with an adjacent R¹⁰, are (CH₂)_(t);

[0194] R¹² is hydrogen or an appropriate amine protecting group fornitrogen or an appropriate carboxylic acid protecting group forcarboxyl;

[0195] R¹³ is independently selected at each occurrence from the groupconsisting of CN, OR¹⁹, SR¹⁹, and C₃-C₆ cycloalkyl;

[0196] R¹⁴ and R¹⁵ are independently selected at each occurrence fromthe group consisting of hydrogen, C₄-C₁₀, cycloalkyl-alkyl, and R₁₉;

[0197] R¹⁷ is independently selected at each occurrence from the groupconsisting of R¹⁰, C₁-C₄ alkoxy, halo, OR²³, SR²³, NR²³R²⁴, and (C₁-C₆)alkyl (C₁-C₄) alkoxy;

[0198] R¹⁸ is independently selected at each occurrence from the groupconsisting of R¹⁰, hydroxy, halogen, C₁-C₂ haloalkyl, C₁-C₄ alkoxy,C(═O)R²⁴, and cyano;

[0199] R¹⁹ is independently selected at each occurrence from the groupconsisting of C₁-C₆ alkyl, C₃-C₆ cycloalkyl, (CH₂)_(w)R²², and arylsubstituted with 0-3 R¹⁸;

[0200] R²⁰ is independently selected at each occurrence from the groupconsisting of R¹⁰, C(═O)R³¹, and C₂-C₄ alkenyl;

[0201] R²¹ is independently selected at each occurrence from the groupconsisting of R¹⁰, C₁-C₄ alkoxy, NR²³R²⁴, and hydroxyl;

[0202] R²² is independently selected at each occurrence from the groupconsisting of cyano, OR²⁴, SR²⁴, NR²³R²⁴, C₁-C₆ alkyl, C₃-C₆ cycloalkyl,—S(O)_(n)R³¹, and —C(═O)R²⁵;

[0203] R²⁵, which can be optionally substituted with 0-3 R17, isindependently selected at each occurrence from the group consisting ofphenyl, pyrazolyl, imidazolyl, 2-methyl-3-pyridinyl,4-methyl-3-pyridinyl, furanyl, 5-methyl-2-furanyl,2,5-dimethyl-3-furanyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl,2-pheno-thiazinyl, 4-pyrazinyl, azetidinyl, 1H-indazolyl,2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl, 2H-pyrrolyl, 3H-indolyl,4-piperidonyl, 4aH-carbazolyl, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl,acridinyl, azocinyl, azepinyl, benzofuranyl, benzothiophenyl,carbazolyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl,furazanyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl,isochromanyl, isoindolinyl, isoindolyl, isoquinolinyl benzimidazolyl,isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl,octahydroisoquinolinyl, oxazolidinyl, oxazolyl, phenanthridinyl,phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathiinyl,phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl,purinyl, pyranyl, pyrazolidinyl, pyridazinyl, pyridyl, pyrimidinyl,pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl,quinoxalinyl, quinuclidinyl, B-carbolinyl, tetrahydrofuranyl,tetrazolyl, thianthrenyl, thiazolyl, thiophenyl, triazinyl, xanthenyl;and 1-tetrahydroquinolinyl or 2-tetrahydroisoquinolinyl either of whichcan be substituted with 0-3 groups chosen from keto and C₁-C₄ alkyl;

[0204] R^(25a), which can be optionally substituted with 0-3 R¹⁷, isindependently selected at each occurrence from the group consisting of Hand R²⁵;

[0205] R²⁷ is independently selected at each occurrence from the groupconsisting of C₁-C₃ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₂-C₄ alkoxy,aryl, nitro, cyano, halogen, aryloxy, and heterocycle optionally linkedthrough 0;

[0206] R³¹ is independently selected at each occurrence from the groupconsisting of C₁-C₄ alkyl, C₃-C₇ cycloalkyl C₄-C₁₀ cycloalkyl-alkyl, andaryl-(C₁-C₄) alkyl;

[0207] k, m, and r are independently selected at each occurrence from1-4;

[0208] n is independently, selected at each occurrence from 0-2,

[0209] p, q, and z are independently selected at each occurrence from0-3;

[0210] t and w are independently selected at each occurrence from 1-6,

[0211] provided that when J is CX′ and K and L are both CH, and M isCR⁵, then

[0212] (A) when V and Y are N and Z is CH and R¹ and R³ are methyl,

[0213] (1) and R⁴ is methyl, then

[0214] (a) R⁵ can not be methyl when X is OH and X′ is H;

[0215] (b) R⁵ can not be —NHCH₃, or —N(CH₃)₂ when X and X′ are —OCH₃;and

[0216] (c) R⁵ can not be —N(CH₃)₂ when X and X′ are —OCH₂CH₃;

[0217] (2) and R⁴ is ethyl, then

[0218] (a) R⁵ can not be methylamine when X and X′ are —OCH₃;

[0219] (b) R⁵ can not be OH when X is Br and X′ is OH; and

[0220] (c) R⁵ can not be —CH₂OH or —CH₂N(CH₃)₂ when X is —SCH₃ and X′ isH;

[0221] (B) when V and Y are N, Z is CH, R⁴ is ethyl, R⁵ is iso-propyl, Xis Br, X′ is H, and

[0222] (1) R¹ is CH₃, then

[0223] (a) R³ can not be OH, piperazin-1-yl, -CH₂,-piperidin-1-yl,—CH₂—(N-4-methylpiperazi n-1-yl), —C(O)NH-phenyl, —CO₂H,—CH₂O—(4-pyridyl), —C(O)NH₂, 2-indolyl, —CH₂O—(4-carboxyphenyl),—N(CH₂CH₃) (2-bromo-4-isopropylphenyl);

[0224] (2) R² is —CH₂CH₂CH₃ then R³ can not be —CH₂CH₂CH₃

[0225] (C) when V, Y and Z are N, R⁴ is ethyl, and

[0226] (1) R⁵ is iso-propyl, X is bromo, and X′ is H, then

[0227] (a) R³ can not be OH or —OCH₂CN when R¹ is CH₃ and

[0228] (b) R³ can not be —N(CH₃)₂ when R¹ is —N(CH₃)₂;

[0229] (2) R⁵ is —OCH₃, X is —OCH₃, and X′ is H, then R³ and R¹ can notboth be chloro;

[0230] further provided that when J, K, and L are all CH and M is CR⁵,then

[0231] (D) at least one of V, Y, and Z must be N;

[0232] (E) when V is CR^(1a), Z and Y can not both be N;

[0233] (F) when Y is CR^(3a), Z and V can not both be N;

[0234] (G) when Z is CR², V and Y must both be N;

[0235] (H) Z can be N only when both V and Y are N or when V is CR^(1a)and Y is CR^(3a);

[0236] (I) when V and Y are N, Z is CR², and R² is H or C₁-C₃ alkyl, andR⁴ is C₁-C₃ alkyl, R³ can not be 2-pyridinyl, indolyl, indolinyl,imidazolyl, 3-pyridinyl, 4-pyridinyl, 2-methyl-3-pyridinyl,4-methyl-3-pyridinyl, furanyl, 5-methyl-2-furanyl,2,5-dimethyl-3-furanyl, 2-thienyl, 3-thienyl, 5-methyl-2-thienyl,2-phenothiazinyl, or 4-pyrazinyl;

[0237] (J) when V and Y are N; Z is CR²; R² is H or C₁-C₃ alkyl; R⁴ isC₁-C₄ alkyl, R⁵, X, and/or X′ are OH, halo, CF₃, C₁-C₄ alkyl, C₁-C₄alkoxy, C₁-C₄ alkylthio, cyano, amino, carbamoyl, or C₁-C₄ alkanoyl; andR¹ is C₁-C₄ alkyl, then R⁴ can not be —NH(substituted phenyl) or—N(C₁-C₄ alkyl) (substituted phenyl);

[0238] and wherein, when Y is CR²⁹:

[0239] J, K, L, M, Z, A, k, m, n, p, q, r, t, w, R³, R¹⁰, R¹¹, R¹², R¹³,R¹⁶, R¹⁸, R¹⁹, R²¹, R²³, R²⁴, R²⁵, and R²⁷ are as defined above andR^(25a), in addition to being as defined above, can also be C₁-C₄ alkyl,but

[0240] V is N;

[0241] R¹ is C₁-C₂ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, C₂-C₄ alkoxy,halogen, amino, methylamino, dimethylamino, aminomethyl, orN-methylaminomethyl;

[0242] R² is independently selected at each occurrence from the groupconsisting of hydrogen, halo, C₁-C₃, alkyl, nitro, amino, and —CO₂R¹⁰);

[0243] R₄ is taken together with R²⁹ to form a 5-membered ring and is—C(R²⁶)═ or —N═ when R²⁹ is —C(R³⁰)═ or —N═, or —CH(R²⁶)— when R²⁹ is—CH(R³⁰)—;

[0244] X is Cl, Br, I, S(O)nR⁸, OR⁸, halomethyl, —(CHR¹⁶)_(p)OR⁸, cyano,—(CHR¹⁶)_(p)NR¹⁴R¹⁵, C(═O)R⁸, C₁-C₆ alkyl, C₂-C₁₀ alkenyl, C₂-C₁₀alkynyl, C₁-C₁₀, alkoxy, aryl-(C₁-C₁₀)-alkyl, C₃-C₆ cycloalkyl,aryl-(C₁-C₁₀)-alkoxy, nitro, thio-(C₁-C₁₀)-alkyl,—C(═NOR¹⁶)-C₁-C₄-alkyl, —C(═NOR¹⁶)H, or C(═O)NR¹⁴R¹⁵ where substitutionby R¹⁸ can occur on any carbon containing substituents;

[0245] X′ is hydrogen, Cl, Br, I, S(O)_(n)R⁸, —(CHR¹⁶)_(p)OR⁸,halomethyl, cyano, —(CHR¹⁶)_(p)NR¹⁴R¹⁵, C(═O)R⁸, C₁-C₆ alkyl,C₂-C₁₀alkenyl, C₂-C₁₀, alkynyl, C₁-C₁₀ alkoxy, aryl-(C₁-C₁₀)-alkyl,C₃-C₆ cycloalkyl, aryl-(C₂-C₁₀)-alkoxy, nitro, thio-(C₂-C₁₀)-alkyl,—C(═NOR¹⁶)-C₁-C₄-alkyl, —C(═NOR¹⁶)H, or C(═O)N R⁸R ¹⁵ where substitutionby R¹⁸ can occur on any carbon containing substituents;

[0246] R⁵ is halo, —C(═NOR¹⁶)—C₁-C₄-alkyl, C₁-C₆ alkyl, C₁-C₃ haloalkyl,C₁-C₆ alkoxy, (CHR¹⁶)_(p)OR⁵, (CHR¹⁶)_(p)S(O)R⁸, (CHR¹⁶)_(p)NR¹⁴R¹⁵,C₃-C₆ cycloalkyl, C₂-C₁₀ alkenyl, C₂-C₁₀ alkynyl, aryl-(C₂-C₁₀)-alkyl,aryl-(C₁-C₁₀)-alkoxy, cyano, C₃-C₆ cycloalkoxy, nitro,amino-(C₁-C₁₀)-alkyl, thio-(C₁-C₁₀)-alkyl, SO_(n)(R⁸), C(═O)R⁸,—C(═NOR¹⁶)H, or C(═O)NR⁸R¹⁵ where substitution by R¹⁸ can occur on anycarbon containing substituents;

[0247] R⁶ and R⁷ are independently selected at each occurrence from thegroup consisting of hydrogen, C₁-C₆ alkyl, C₃-C₁₀ cycloalkyl,—(CH₂)_(k)R¹³, (C₄-C₁₂)-cycloalkylalkyl, C₁-C₆ alkoxy, -(C₁-C₆alkyl)-aryl, heteroaryl, aryl, —S(O)_(z)-aryl or —(C₁-C₆alkyl)-heteroaryl or aryl wherein the aryl or heteroaryl groups areoptionally substituted with 1-3 groups selected from hydrogen, halogen,C₁-C₆ alkyl, C₁-C₆ alkoxy, amino, NHC(═O)(C₁-C₆ alkyl), NH(C₁—C₆ alkyl),N(C₁-C₆ alkyl)₂, nitro, carboxy, CO₂(C₁-C₆ alkyl), and cyano; or can betaken together to form —(CH₂)qA(CH₂)_(r)—, optionally substituted with0-3 R¹⁷; or, when considered with the commonly attached nitrogen, can betaken together to form a heterocycle, said heterocycle being substitutedon carbon with 1-3 groups consisting of hydrogen, C₁-C₆ alkyl, hydroxy,or C₁-C₆ alkoxy;

[0248] R⁸ is independently selected at each occurrence from the groupconsisting of hydrogen, C₁-C₆ alkyl, —(C₄-C₁₂) cycloalkylalkyl,(CH₂)_(t)R²², C₃-C₁₀ cycloalkyl, —(C₁-C₆ alkyl)-aryl, heteroaryl, —NR¹⁶,—N(CH₂)_(n)NR⁶R⁷; —(CH₂)_(k)R²⁵, —(C₁-C₆ alkyl)-heteroaryl or aryloptionally substituted with 1-3 groups selected from hydrogen, halogen,C₁-C₆ alkyl, C₁-C₆ alkoxy, amino, NHC(═O)(C₁-C₆ alkyl), NH(C₁-C₆ alkyl),N(C₁-C₆alkyl)₂, nitro, carboxy, CO₂(C₁-C₆ alkyl), and cyano;

[0249] R⁹ is independently selected at each occurrence from R¹⁰,hydroxy, C₁-C₄ alkoxy, C₃-C₆ cycloalkyl, C₂-C₄ alkenyl, and arylsubstituted with 0-3 R¹⁸;

[0250] R¹⁴ and R¹⁵ are independently selected at each occurrence fromthe group consisting of hydrogen, C₁-C₆ alkyl, C₃-C₆ cycloalkyl,(CH₂)_(t)R²², and aryl substituted with 0-3 R¹⁸;

[0251] R¹⁷ is independently selected at each occurrence from the groupconsisting of R¹⁰, C₁-C₄ alkoxy, halo, OR²³, SR²³, and NR²³R²⁴;

[0252] R²⁰ is independently selected at each occurrence from the groupconsisting of R¹⁰ and C(═O)R³¹;

[0253] R²² is independently selected at each occurrence from the groupconsisting of cyano, OR²⁴, SR²⁴, NR²³R²⁴, C₃-C₆ cycloalkyl,—S(O)_(n)R³¹, and —C(═O)R ²⁵;

[0254] R²⁶ is hydrogen or halogen;

[0255] R²⁸ is C₁-C₂, alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, hydrogen,C₁-C₂ alkoxy, halogen, or C₂-C₄ alkylamino;

[0256] R²⁹ is taken together with R⁴ to form a five membered ring andis: —CH(R³⁰)— when R⁴ is —CH(R²⁸)—, —C(R³⁰)═ or —N═ when R⁴ is —C(R²⁸)═or —N═;

[0257] R³⁰ is hydrogen, cyano, C₁-C₂ alkyl, C₁-C₂ alkoxy, halogen, C₁-C₂alkenyl, nitro, amido, carboxy, or amino;

[0258] R³¹ is C₁-C₄ alkyl, C₃-C₇ cycloalkyl, or aryl-(C₁-C₄) alkyl;provided that when J, K, and L are all CH, M is CR⁵, Z is CH, R³ is CH₃,R²⁸ is H, R⁵ is isopropyl, X is Br, X′ is H, and R′ is CH₃, then R³⁰ cannot be H, —CO₂H, or —CH₂NH₂; and further

[0259] provided that when J, K and L are all CH; M is CR⁵; Z is N; and

[0260] (A) R²⁹ is —C(R³⁰)═; then one of R²⁸ or R³⁰ is hydrogen;

[0261] (B) R²⁹ is N; then R³ is not halo, NH₂, NO₂, CF₃, CO₂H,CO₂-alkyl, alkyl, acyl, alkoxy, OH, or —(CH₂)_(m)O alkyl;

[0262] (C) R²⁹ is N; then R²⁸ is not methyl if X or X′ are bromo ormethyl and R⁵ is nitro; or

[0263] (D) R²⁹ is N; and R¹ is CH₃; and R³is amino; then R⁵ is nothalogen or methyl.

[0264] Preferred compounds of this group include those wherein:

[0265] i) V is N, R¹ is methyl; and R³ is aryl, NR⁶R⁷, or OR⁸;

[0266] ii) V is N, R¹ is methyl; R³ is aryl, NR⁶R⁷, or OR⁸; and R⁴ ismethyl or ethyl;

[0267] iii) V is N, R¹ is methyl; R³ is aryl, NR⁶R⁷, or OR⁸; R⁴ ismethyl or ethyl; and X is O(C₁-C₄ alkyl), Br, or C₁-C₄ alkyl;

[0268] iv) V is N, R¹ is methyl; R³ is aryl, NR⁶R⁷, or OR⁸; R⁴ ismethyl, ethyl; X is OMe, Br, or (C₁-C₄ alkyl), M is C₁-C₄ alkyl, Br, Cl,or O (C₁-C₄ alkyl); and

[0269] v) V is N, R¹ is methyl; R³ is aryl, NR⁶R⁷, OR⁸; or R⁴ is methyl,ethyl; X is OMe, Br, or C₁-C₄ alkyl, M is C₁-C₄ alkyl, Br, Cl, or O(C₁-C₄ alkyl); and L is CH, or N.

[0270] X. The invention also encompasses use of aminothiazolederivatives of the following formula, disclosed in WO 97/00868:

[0271] wherein each of R¹ and R² is independently a halogen atom; aC₁-C₅ hydroxyalkyl radical; C₁-C₅ alkyl; C₇-C₁₀ aralkyl; C₁-C₅ alkoxy;trifluoromethyl; nitro; nitrile; a group —SR where R is hydrogen, aC₁-C₅ alkyl radical or a C₇-C₁₀ aralkyl radical; a group S—CO—R where Ris a C₁-C₅ alkyl radical or aralkyl in which the aryl portion is C₆-C₈and the alkyl portion is C₁-C₄; a group —COOR′ where R′ is hydrogen orC₁-C₅ alkyl; a group —CONR′R″ where R′ and R″ are as defined above forR′; a group —NR′R″ where R′ and R″ are as previously defined for R′; agroup —CONRaRb or NRaRb, where Ra and Rb, taken together with thenitrogen atom to which they are attached, form a 5- to 7-memberedheterocyclic ring; or a group—NHCO—NR′R″, where R′ and R″ are as definedabove for R′; R³ is hydrogen or as defined for R¹ and R² is a hydrogenatom; C₁₋₅alkyl; halogen; a hydroxymethyl group; or a formyl group; R⁵is C₁-C₅ alkyl; a C₃-C₇ cycloalkyl group; a cycloalkylalkyl group inwhich the cycloalkyl portion is C₃-C₇ and the alkyl portion is C₁-C₅; orC₅-C₆ alkenyl; n is 0 or 1; R⁶ is C, ₅ alkyl; alkoxyalkyl in which thealkyl portions are C₁-C₅; C₃-C₇ cycloalkyl; a cycloalkylalkyl group inwhich the cycloalkyl portion is C₃-C₇ and the alkyl portion is C₁-C₅; acycloalkyloxyalkyl radical in which the cycloalkyl is C₃-C₇ and thealkyl is C₁-C₄; a hydroxyalkyloxyalkyl radical in which the alkyls areC₂-C₁₀; or an alkoxyalkyloxyalkyl radical in which the alkyls areC₃-C₁-₂; and Z is an optionally substituted bi- or tricyclic aromatic orheteroaromatic group; and stereoisomers and/or addition salts thereof.

[0272] XI. CRF antagonists of the following formula, disclosed in WO97/29109, may also be employed:

[0273] including the stereoisomers and the pharmaceutically acceptableacid addition salt forms thereof, wherein

[0274] R¹ is NR⁴R⁵ or OR⁵;

[0275] R² is C₁-C₆alkyl, C₁-C₆alkyloxy or C₁-C₆alkylthio,

[0276] R³ is hydrogen, C₁-C₆alkyl, C₁-C₆alkylsulfonyl, C₁-C₆alkylsulfoxyor C₁-C₆alkylthio;

[0277] R⁴ is hydrogen, C₁-C₆alkyl, mono- or di(C₃-C₆cyloalkylmethyl,C₃-C₆cyloalkyl, C₃-C₆alkenyl, hydroxyC₁-C₆alkyl,C₁-C₆akylcarbonyloxyC₁-C₆alkyl or C₁-C₆alkyloxyC₁-C₆alkyl;

[0278] R⁵ is C₁-C₈alkyl, mono- or di(C₃-C₆cycloalkyl)methyl, Ar¹CH₂,C₃-C₆alkenyl, C₁-C₆alkyloxyC₁-C₆alkyl, hydroxyC₁-C₆alkyl, thienylmethyl,furanylmethyl, C₁-C₆alkylthioC₁-C₆alkyl, morpholinyl, mono- ordi(C₁-C₆alkyl)aminoC₁₋₆alkyl, di(C₁-C₆alkyl)amino,C₁-C₆alkylcarbonylC₁-C₆alkyl, C₁-C₆alkyl substituted with imidazolyl; ora radical of formula —Alk—O—CO—Ar¹;

[0279] or R⁴ and R⁵ taken together with the nitrogen atom to which theyare attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl ormorpholinyl group, optionally substituted with C₁-C₆alkyl orC₁-C₆alkyloxyC₁-C₆alkyl; and

[0280] Ar is phenyl; phenyl substituted with 1, 2 or 3 substituentsindependently selected from halo, C₁-C₆alkyl, trifluoromethyl, hydroxy,cyano, C₁-C₆alkyloxy, benzyloxy, C₁-C₆alkylthio, nitro, amino and mono-or di(C₁-C₆alkyl)amino; pyridinyl; pyridinyl substituted with 1˜2 or 3substituents independently selected from halo, C₁-C₆alkyl,trifluoromethyl, hydroxy, cyano, C₁-C₆alkyloxy, benzyloxy,C₁-C₆alkylthio, nitro, amino, mono- or di(C₁-C₆alkyl)amino andpiperidinyl; and wherein said substituted phenyl may optionally befurther substituted with one or more halogens;

[0281] Ar¹ is phenyl; phenyl substituted with 1, 2 or 3 substituentseach independently selected from halo, C₁-C₆alkyl, C₁-C₆alkyloxy,di(C₁-C₆alkyl)aminoC₁-C₆alkyl, trifluoromethyl and C₁-C₆alkylsubstituted with morpholinyl; or pyridinyl; and

[0282] Alk is C₁-C₆alkanediyl;

[0283] with the proviso that

[0284] 5-methyl-3-phenyl-7-(phenylmethoxy)-pyrazolo[1,5-a]-pyrimidineand 2,5-dimethyl-7-(methylamino)-3-phenyl-pyrazolo[1,5-a]pyrimidine arenot included.

[0285] Preferred compounds of this formula are those wherein R² ismethyl; R³ is hydrogen, or C₁-C₆ alkyl; and Ar is substituted phenyl or3-pyridyl.

[0286] XII. CRF antagonists of the following formula, disclosed in WO97/29110, may also be employed:

[0287] including the stereoisomers and the pharmaceutically acceptableacid addition salt forms thereof, wherein

[0288] X is S, SO or S0₂;

[0289] R¹ is NR⁴R⁵ or OR⁵;

[0290] R² is C₁-C₆alkyl, C₁-C₆alkyloxy or C₁-C₆alkylthio;

[0291] R³ is hydrogen, C₁-C₆alkyl, C₁-C₆alkylsulfonyl, C₁-C₆alkylsulfoxyor C₁-C₆alkylthio;

[0292] R⁴ is hydrogen, C₁₋₆alkyl, mono- or di(C₃-C₆cycloalkyl)methyl,C₃-C₆cycloalkyl, C₃-C₆alkenyl, hydroxyC₁-C₆alkyl,C₁-C₆alkylcarbonyloxyC₁-C₆alkyl or C₁-C₆alkyloxyC₁-C₆alkyl;

[0293] R⁵ is C₁-C₈alkyl, mono- or di(C₃-C₆cycloalkyl)methyl, Ar¹CH₂,C₃-C₆alkenyl, C₁-C₆alkyloxyC₁-C₆alkyl, hydroxyC₁-C₆alkyl, thienylmethyl,furanylmethyl, C₁-C₆alkylthioC₁-C₆alkyl, morpholinyl, mono- ordi(C₁-C₆alkyl)aminoC₁-C₆alkyl, di(C₁-C₆alkyl)amino,C₁-C₆alkylcarbonylC₁-C₆alkyl, C₁-C₆alkyl substituted with imidazolyl; ora radical of formula —Alk—O—CO—Ar I;

[0294] or R⁴ and R⁵ taken together with the nitrogen atom to which theyare attached may form a pyrrolidinyl, piperidinyl, homopiperidinyl ormorpholinyl group, optionally substituted with C₁-C₆alkyl orC₁-C₆alkyloxyC₁-C₆alkyl;

[0295] Ar is phenyl; phenyl substituted with 1, 2 or 3 substituentsindependently selected from halo, C₁-C₆alkyl, trifluoromethyl, hydroxy,cyano, C₁-C₆alkyloxy, benzyloxy, C₁-C₆alkylthio, nitro, amino and mono-or di(C₁-C₆alkyl)amino; pyridinyl; pyridinyl substituted with 1, 2 or 3substituents independently selected from halo, C₁-C₆alkyl,trifluoromethyl, hydroxy, cyano, C₁-C₆alkyloxy, benzyloxy,C₁-C₆alkylthio, nitro, amino, mono- or di(C₁-C₆alkyl)amino andpiperidinyl; and wherein said substituted phenyl may optionally befurther substituted with one or more halogens;

[0296] Ar¹ is phenyl; phenyl substituted with 1, 2 or 3 substituentseach independently selected from halo, C₁-C₆alkyl, C₁-C₆alkyloxy,di(C₁-C₆alkyl)aminoC₁-C₆alkyl trifluoromethyl, and C₁-C₆alkylsubstituted with morpholinyl; or pyridinyl; and

[0297] Alk is C₁-C₆alkanediyl.

[0298] Preferred compounds of this group include those wherein:

[0299] i) R² is methyl;

[0300] ii) R² is methyl; and Ar is substituted phenyl or 3-pyridyl;

[0301] iii) R² is methyl; R³ is methyl; and Ar is substituted phenyl or3-pyridyl

[0302] XIII. CRF antagonists of the following formula, disclosed in EP0773023, may also be employed:

[0303] or a pharmaceutically acceptable salt thereof, wherein

[0304] the dashed line represents an optional double bond;

[0305] A is —CR₇ or N;

[0306] B is —NR₁R₂, —CR₁R₂R₁₁, —C(═CR₁R₁₂)R₂, —NHCR₁₁R₁R₂, —OCR₁₁R₁R₂,—SCR₁₁R₁R₂, —CR₁₁R₂OR₁, —CR₁₁R₂SR₁, —C(S)R₂, —NHNR₁R₂, —CR₂R₁₁NHR₁ or—C(O)R₂;

[0307] D is N or —CR₁₀ when a double bond connects E and D and E is—CR₄; —CR₁₀ when a double bond connects E and D and E is N; or —CR₈R₉,—CHR₁₀, —C═O, —C═S, —C═NH, or —C═NCH₃ when a single bond connects E andD;

[0308] E is —CR₄ or N when a double bond connects E and D, and E is—CR₄R₆ or —NR₆ when a single bond connects E and D;

[0309] Y is N or —CH;

[0310] Z is NH, O, S, —N(C₁-C₂ alkyl), or —CR₁₂R₁₃, wherein R₁₂ and R₁₃are each, independently, hydrogen, trifluoromethyl, or methyl, or one ofR₁₂ and R₁₃ is cyano and the other is hydrogen or methyl;

[0311] R₁ is hydrogen or C₁-C₆ alkyl which is optionally substitutedwith up to two substituents independently selected from hydroxy, cyano,nitro, fluoro, chloro, bromo, iodo, CF₃, C₁-C₄ alkoxy, —O—CO—(C₁-C₄alkyl), —O—CO—NH(C₁-C₄ alkyl), —O—CO—N(C₁-C₄ alkyl)(C₁-C₂ alkyl),—NH(C₁-C₄ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —S(C₁-C₄ alkyl),—N(C₁-C₄alkyl)CO(C₁-C₄ alkyl), -NHCO(C₁-C₄ alkyl), —CO₂(C₁-C₄ alkyl),—CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), (C₁-C₄alkyl)sulfinyl, (C₁-C₄ alkyl)sulfonyl, and (C₁-C₄ alkyl)sulfanyl, andwherein said C₁-C₆ alkyl, C₁-C₄ alkoxy, and C₁-C₄ alkyl moieties in theforegoing R₁ groups optionally contain one double or triple bond;

[0312] R₂ is C₁-C₆ alkyl, heteroaryl, aryl, heteroaryl (C₁-C₄ alkyl), oraryl (C₁-C₄ alkyl), wherein said aryl and the aryl moiety of said(aryl)C₁-C₄ alkyl are selected from the group consisting of phenyl andnaphthyl, and said heteroaryl and the heteroaryl moiety of said(heteroaryl)C₁-C₄ alkyl is selected from the group consisting ofthienyl, benzothienyl, pyridyl, thiazolyl, quinolyl, pyrazinyl,pyrimidyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, indolyl,and benzoxazolyl; or R² is C₃-C₈ cycloalkyl or (C₃-C₈ cycloalkyl)C₁-C₆alkyl, wherein one or two of the ring carbons of said cycloalkyl havingat least 4 ring members and the cycloalkyl moiety of said (C₃-C₈cycloalkyl)C₁-C₆ alkyl having at least 4 ring members is optionallyreplaced by an oxygen or sulfur atom or by —NR₁₄ wherein R₁₄ is hydrogenor C₁-C₄ alkyl; and wherein each of the foregoing R₂ groups isoptionally substituted by up to three substituents independentlyselected from chloro, fluoro, and C₁-C₄ alkyl, or by one substituentselected from bromo, iodo, cyano, nitro, C₁-C₆ alkoxy, —O—CO—(C₁-C₄alkyl), —CO—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —CO₂(C₁-C₄ alkyl), (C₁-C₄alkyl)sulfanyl, (C₁-C₄ alkyl)sulfinyl, and (C₁-C₄ alkyl)sulfanyl, andwherein said C₁-C₄ alkyl and C₁-C₆ alkyl moieties of the foregoing R₂groups optionally contain one carbon-carbon double or triple bond;

[0313] or R¹ and R² of said —NR₁R₂ and said —CR₁R₂R₁₁ are taken togetherto form a saturated or partially saturated 5- to 8-membered ring,wherein said ring optionally contains one or two carbon-carbon doublebonds, and wherein one or two of the ring carbons is optionally replacedby a heteroatom selected from O, S, and N;

[0314] R₃ is hydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo,hydroxy, amino, SH, —NH(C₁-C₄ alkyl), —N(C₁-C₄ alkyl)(C₁-C₂ alkyl),—CH₂OH, —CH₂OCH₃, —O(C₁-C₄ alkyl), (C₁-C₄ alkyl)sulfanyl, (C₁-C₄alkyl)sulfonyl, or (C₁-C₄ alkyl)sulfinyl, wherein said C₁-C₆ alkyl andC₁-C₄ alkyl moieties of the foregoing R₃ groups optionally contain onedouble or triple bond and are optionally substituted by from one tothree substituents independently selected from hydroxy, amino, C₁-C₃alkoxy, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)₂, —NHCOCH₃, fluoro, chloro,and C₁-C₃ thioalkyl;

[0315] R₄ is hydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo, C₁-C₆alkoxy, formyl, trifluoromethoxy, —CH₂OCH₃, —CH₂OCH₂CH₃, —CH₂CH₂OCH₃,—CH₂CF₃, CF₃, amino, nitro, —NH(C₁-C₄ alkyl), —N(CH₃)₂, —NHCOCH₃,—NHCONHCH₃, (C₁-C₄ alkyl)sulfanyl, (C₁-C₄ alkyl)sulfinyl, (C₁-C₄alkyl)sulfonyl, cyano, hydroxy, —CO(C₁-C₄ alkyl), —CHO, or —CO₂(C₁-C₄alkyl), wherein said C₁-C₆ alkyl, C₁-C₆ alkoxy, and C₁-C₄ alkyl moietiesof the foregoing R₄ groups optionally contain one double or triple bondand are optionally substituted with one substituent selected fromhydroxy, amino, —NHCOCH₃, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)₂, —O₂(C₁-C₄alkyl), —CO(C₁-C₄ alkyl), C₁-C₃ alkoxy, (C₁-C₃ alkyl)sulfanyl, fluoro,chloro, cyano, and nitro;

[0316] R₅ is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinolyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl,benzothiazolyl, isothiazolyl, benzoisothiazolyl, thiazolyl, isoxazolyl,benzisoxazolyl, benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl,azaindolyl, benzoxazolyl, oxazolyl, pyrrolidinyl, thiazolidinyl,morpholinyl, pyridinyl, tetrazolyl, or a 3- to 8-membered cycloalkylring or a 9- to 12-membered bicycloalkyl ring system, wherein saidcycloalkyl ring and said bicycloalkyl ring system optionally contain oneor two of O, S, or —N—G wherein G is hydrogen, C₁-C₄ alkyl, C₁-C₄alkanoyl, phenyl, or benzyl, wherein each of the above R₅ groups isoptionally substituted by up to three substituents independentlyselected from fluoro, chloro, C₁-C₆ alkyl, C₁-C₆ alkoxy, andtrifluoromethyl, or one substituent selected from bromo, iodo, cyano,nitro, amino, —NH(C₁-C₄ alkyl), —N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —CO₂(C₁-C₄alkyl), —CO(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl), —SO₂N(C₁-C₄ alkyl)(C₁-C₂alkyl), —SO₂NH₂, —NHSO₂(C₁-C₄ alkyl), —S(C₁-C₄ alkyl), and —SO₂(C₁-C₄alkyl), wherein said C₁-C₄ alkyl and C₁-C₆ alkyl moieties of theforegoing R₅ groups optionally contain one double or triple bond and areoptionally substituted by one or two substituents independently selectedfrom fluoro, chloro, hydroxy, amino, methylamino, dimethylamino, andacetyl;

[0317] R₆ is hydrogen or C₁-C₆ alkyl, wherein said C₁-C₆ alkyl isoptionally substituted by a single hydroxy, methoxy, ethoxy, or fluorogroup;

[0318] R₇ is hydrogen, C₁-C₄ alkyl, fluoro, chloro, bromo, iodo, cyano,hydroxy, C₁-C₄ alkoxy, —CO(C₁-C₄ alkyl), —CO₂(C₁-C₄ alkyl), —OCF₃, CF₃,—CH₂OH, —CH₂OCH₃, or —CH₂OCH₂CH₃;

[0319] R₈ and R₉ are each, independently, hydrogen, hydroxy, methyl,ethyl, methoxy, or ethoxy;

[0320] or R₈ and R₉ together form an oxo (═O) group;

[0321] R₁₀ is hydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo, C₁-C₆alkoxy, formyl, amino, —NH(C₁-C₄ alkyl), —N(C₁-C₄ alkyl)(C₁-C₂ alkyl),cyano, carboxy, amido, or —SO_(n)(C₁-C₄ alkyl) wherein n is 0, 1, or 2,wherein said C₁-C₆ alkyl and C₁-C₄ alkyl moieties of the foregoing R₁₀groups are optionally substituted by one of hydroxy, trifluoromethyl,amino, carboxy, amido, —NHCO(C₁-C₄ alkyl), —NH(C₁-C₄ alkyl), —N(C₁-C₄alkyl)(C₁-C₂ alkyl), —CO₂(C₁-C₄ alkyl), C₁-C₃ alkoxy, C₁-C₃ thioalkyl,fluoro, bromo, chloro, iodo, cyano, or nitro; and

[0322] R₁₁ is hydrogen, hydroxy, fluoro, or methoxy.

[0323] Specific CRF antagonists useful in the practice of the presentinvention, include, without limitation, the following compounds:

[0324]4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine;

[0325]butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-ethyl-amine;

[0326]4-(butyl-ethylamino)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one;

[0327]4-(1-ethylpropoxy)-2,5-dimethyl-6-(2,4,6-trimethylphenoxy)-pyrimidine;

[0328]N-butyl-N-ethyl-2,5-dimethyl-NN-(2,4,6-trimethylphenyl)-pyrimidine-4,6-diamine;

[0329][4-(1-ethyl-propoxy)-3,6-dimethyl-pyridin-2-yl]-(2,4,6-trimethylphenyl)-amine;

[0330]6-(ethyl-propyl-amino)-2,7-dimethyl-9-(2,4,6-trimethylphenyl)-7,9-dihydro-purin-8-one;

[0331]3-{(4-methyl-benzyl)-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-propan-1-ol;

[0332]diethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino;

[0333]2-{butyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-ethanol;

[0334]dibutyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl}-amine;

[0335]butyl-ethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0336]butyl-ethyl-[6-methyl-3-methylsulfonyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0337]butyl-cyclopropylmethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0338]di-1-propyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0339]diallyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0340]butyl-ethyl-[6-chloro-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0341]butyl-ethyl-[6-methoxy-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0342]propyl-ethyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0343]4-(1-ethyl-propyl)-6-methyl-3-methylsulfanyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidine;

[0344]n-butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;

[0345]di-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;

[0346]ethyl-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;

[0347]diethyl-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;

[0348]n-butyl-ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;

[0349]2-{N-n-butyl-N-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-ethanol;

[0350]4-(1-ethyl-propyl)-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidine;

[0351]n-butyl-ethyl-[2,5-dimethyl-7-(2,4-dimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;

[0352]2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidyl-4-yl]-(1-ethyl-propyl)amine;

[0353]butyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-ethylamine;

[0354][3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4,b]pyridin-4-yl]-(1-methoxymethylpropyl)-amine;

[0355]4-(1-methoxymethylpropoxy)-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine;

[0356](1-ethylpropyl)-[3,5,6-trimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-amine;

[0357]4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;

[0358]4-(1-ethylpropoxy)-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;

[0359]4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,6-dimethyl-4-bromophenyl)-7H-pyrrolo[2,3-b]pyridine;

[0360]2,5,6-trimethyl-7-(1-propylbutyl)-4-(2,4,6-trimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine;

[0361]1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenylamino)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;

[0362]9-(1-ethylpropyl)-2-methyl-6-(2,4,6-trimethylphenylamino)-7,9-dihydro-purin-8-one;

[0363]1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;

[0364]1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1H-imidazo[4,5-c]pyridine;

[0365]1-(1-ethylpropyl)-3,6-dimethyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;

[0366]1-(1-ethylpropyl)-3,6-dimethyl-4-(2,4,6-trimethylphenylamino)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;

[0367]1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one;

[0368]1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;

[0369]1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;

[0370]1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid methyl ester;

[0371]1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid isopropyl ester;

[0372]1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-3,4-dihydro-1H-[1,6]naphthyridin-2-one;

[0373]1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-[1,6]naphthyridine;

[0374]1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;

[0375]1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;

[0376]1-(1-ethyl-propyl)-3,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-3,4-dihydro-1H-3-oxa-[1,6]-naphthyridin-2-one;

[0377]1-(1-ethyl-propyl)-3,3,6-trimethyl-4-(2,4,6-trimethyl-phenoxy)-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine;

[0378]7-(1-ethyl-propoxy)-5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;

[0379][2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;

[0380](1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine;

[0381]7-(1-ethyl-propoxy)-2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;

[0382][2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-ethyl-propyl-amine;

[0383][6-bromo-5-bromomethyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-(1-ethyl-propyl)-amine;

[0384](1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-amine;

[0385][6-bromo-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-(1-ethyl-propyl)-methyl-amine;

[0386]7-(1-ethyl-propoxy)-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridine;

[0387]4-(1-ethyl-propoxy)-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;

[0388](±)-2,5-dimethyl-4-(tetrahydro-furan-3-yloxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo-[3,2-d]pyrimidine;

[0389]2,5-dimethyl-4-(S)-(tetrahydro-furan-3-yloxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo-[3,2-d]pyrimidine;

[0390]2,5-dimethyl-4-(1-propyl-butoxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;

[0391]4-sec-butylsulfanyl-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;

[0392]4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;

[0393]8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0394]8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0395]4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0396]5-(1-ethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0397]5-(1-ethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;

[0398]8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0399](1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-quinolin-4-yl]-amine;

[0400]4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;

[0401]4-(butyl-ethyl-amino)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;

[0402]4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;

[0403](butyl-ethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;

[0404](propyl-ethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;

[0405](diethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;

[0406](1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;

[0407](1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;

[0408]4-(butyl-ethyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;

[0409]4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;

[0410](butyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;

[0411](propyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidin-4-yl]-amine;

[0412](diethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;

[0413](1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;

[0414](1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;

[0415]8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-bromo-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0416]8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-bromo-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0417]4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-quinoline;

[0418]5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-bromo-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0419]5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-bromo-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;

[0420]8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,6-dimethyl-4-bromo-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0421](1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-quinolin-4-yl]-amine;

[0422]4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,6-dimethyl-4-chloro-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;

[0423]8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-chloro-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0424]8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-chloro-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0425]4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-chloro-phenyl)-quinoline;

[0426]5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-chloro-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0427]5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-chloro-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;

[0428]8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,6-dimethyl-4-chloro-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0429](1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-chloro-phenyl)-quinolin-4-yl]-amine;

[0430]8-(1-hydroxymethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0431]8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0432]8-(1-ethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0433]8-diethylamino-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido-[2,3-b]pyrazin-2-one;

[0434]8-(ethyl-propyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0435]8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0436]8-(1-hydroxymethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0437]8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0438]8-(1-ethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0439]8-diethylamino-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0440]8-(ethyl-propyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0441]8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0442]4-(1-hydroxymethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0443]4-(1-hydroxymethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0444]4-(1-ethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0445] 4-diethylamino-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0446]4-(ethyl-propyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0447]4-(butyl-ethyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0448]5-(1-hydroxymethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0449]5-(1-hydroxymethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0450]5-(1-ethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0451]5-diethylamino-5-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0452]5-(ethyl-propyl-amino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0453]8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0454]4-(2,4-dichlorophenyl)-5-methyl-2-[N-(1-(methoxymethyl)-1-(naphth-2-yl)-methyl)-N-propylamino]thiazole;

[0455] oxalate of4-(2,4-dichlorophenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;

[0456] oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methylisoquinol-5-yl)-N-propylamino]thiazole;

[0457]4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-methoxycarbonylmethylindol-5-yl)-N-propylamino]thiazole;

[0458] oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;

[0459] oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-chloroisoquinol-5-yl)-N-propylamino]thiazole;

[0460] oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;

[0461]4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-1-methoxynaphth-2-yl)-N-propylamino]thiazole;

[0462] oxalate of4-(2-chloro-4-trifluoromethylphenyl)-5-methyl-2-[N-6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;

[0463] chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(2-ethoxynaphth-1-yl)-N-propylamino]thiazole;

[0464] chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2[N-(2,3-dimethylnaphth-1-yl)-N-propylamino]thiazole;

[0465] chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-bromo-2-methoxynaphth-1-yl)-N-propylamino]thiazole;

[0466] chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(2,6-dimethylnaphth-1-yl)-N-propylamino]thiazole;

[0467] chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-(methoxymethyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;

[0468] chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-(cyclopropyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;

[0469]3-(2,4-dichlorophenyl)-5-methyl-7(N-propyl-N-cyclopropanemethylamino)-pyrazolo[2,3-a]pyrimidine;

[0470]3-(2,4-dichlorophenyl)-5-methyl-7-(N-allyl-N-cyclopropanemethylamino)-pyrazolo[2,3-a]pyrimidine;

[0471]2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N,N-diallylamino)-pyrazolo[2,3-a]pyrimidine;

[0472]2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N-butyl-N-cyclopropane-methyl-amino)pyrazolo[2,3-a]pyrimidine;

[0473]2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N-propyl-N-cyclopropane-methyl-amino)pyrazolo[2,3-a]pyrimidine;

[0474]2-methyl-3-(4-chlorophenyl)-5-methyl-7-(N,N-dipropylamino)-pyrazolo[2,3-a]pyrimidine;

[0475]3-[6-(dimethylamino)-3-pyridinyl]-2,5-dimethyl-N,N-dipropylpyrazolo[2,3-a]pyrimidin-7-amine;

[0476]3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidine-7-amine;

[0477]3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo[2,3-a]pyrimidine;

[0478]3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N-propyl-N-cyclopropylmethyl-pyrazolo[2,3-a]pyrimidin-7-amine;

[0479]3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N-ethyl-N-cyclopropylmethyl-pyrazolo[2,3-a]pyrimidin-7-amine;

[0480]7-(N-diethylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine;

[0481]7-(N-(3-cyanopropyl)-N-propylamino-2,5,dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]-pyrazolopyrimidine;

[0482][3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl]-(1-ethyl-propyl)-amine;

[0483][2-(4-chloro-2,6-dimethyl-phenoxy)-3,6-dimethyl-pyridin-4-yl]-(1-ethyl-propyl)-amine;

[0484]cyclopropylmethyl-[3-(2,4-dimethyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;

[0485]cyclopropylmethyl-[3-(2-methyl-4-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;

[0486]cyclopropylmethyl-[3-(2,4-di-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;

[0487][3-(2-methyl-4-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-di-propyl-amine;

[0488][2,5-dimethyl-3-(2,4-dimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;

[0489][2,5-dimethyl-3-(2,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;and

[0490]4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-nicotinicacid methyl ester.

[0491] Even more particularly, specific CRF antagonists useful in thepractice of the present invention include, without limitation, thefollowing compounds:

[0492]4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine;

[0493]4-(1-ethylpropoxy)-2,5-dimethyl-6-(2,4,6-trimethylphenoxy)-pyrimidine;

[0494][4-(1-ethyl-propoxy)-3,6-dimethyl-pyridin-2-yl]-(2,4,6-trimethylphenyl)-amine;

[0495]3-{(4-methyl-benzyl)-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-propan-1-ol;

[0496]propyl-ethyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;

[0497]ethyl-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;

[0498]2-{N-n-butyl-N-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-ethanol;

[0499][3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4,b]pyridin-4-yl]-(1-methoxymethylpropyl)-amine;

[0500]4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;

[0501]2,5,6-trimethyl-7-(1-propylbutyl)-4-(2,4,6-trimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine;

[0502]1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;

[0503]1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one;

[0504]1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;

[0505]1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid isopropyl ester;

[0506]1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;

[0507](1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine;

[0508]7-(1-ethyl-propoxy)-2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;

[0509]4-(1-ethyl-propoxy)-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;

[0510]4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;

[0511]8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;

[0512]4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0513](1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-quinolin-4-yl]-amine;

[0514](propyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidin-4-yl]-amine;

[0515](1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;

[0516]8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;

[0517]4-(1-hydroxymethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;

[0518]5-(1-hydroxymethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;

[0519][3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl]-(1-ethyl-propyl)-amine;

[0520]cyclopropylmethyl-[3-(2,4-dimethyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;

[0521][2,5-dimethyl-3-(2,4-dimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;

[0522]3-[6-(dimethylamino)-3-pyridinyl-2,5-dimethyl-N,N-dipropylpyrazolo[2,3-a]pyrimidin-7-amine;

[0523]3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidine-7-amine;

[0524]3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo(2,3-a)pyrimidine;

[0525]7-(N-diethylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine;

[0526]7-(N-(3-cyanopropyl)-N-propylamino-2,5,dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]-pyrazolopyrimidine.

[0527] Methods for making the CRF antagonists described above aredisclosed in the above-listed patents and published patent applicationsincorporated by reference herein.

[0528] In one aspect of the present invention, a CRF antagonist may beused in combination with a GR antagonist. The glucocorticoid receptor(GR) is present in glucocorticoid responsive cells where it resides inthe cytosol in an inactive state until it is stimulated by an agonist.Upon stimulation the glucocorticoid receptor translocates to the cellnucleus where it specifically interacts with DNA and/or protein(s) andregulates transcription in a glucocorticoid responsive manner. Twoexamples of proteins that interact with the glucocorticoid receptor arethe transcription factors, API and NFκ-B. Such interactions result ininhibition of API-and NFκ-B-mediated transcription and are believed tobe responsible for the anti-inflammatory activity of endogenouslyadministered glucocorticoids. In addition, glucocorticoids may alsoexert physiologic effects independent of nuclear transcription.Biologically relevant glucocorticoid receptor agonists include cortisoland corticosterone. Many synthetic glucocorticoid receptor agonistsexist including dexamethasone, prednisone and prednisilone. As definedabove, a glucocorticoid receptor (GR) antagonist refers to a compoundthat binds to the receptor and prevents a glucocorticoid receptoragonist from binding and eliciting GR mediated events, includingtranscription. RU486 is an example of a non-selective glucocorticoidreceptor antagonist.

[0529] Any GR antagonist can be used to practice the present invention,including those that are described in commonly assigned : Internationalpatent application PCT/IB00/00366, filed Mar. 27, 2000; U.S. Pat. No.5,696,127; International patent publications WO 99/41256 and WO99/41257; U.S. Pat. No. 5,696,127; European patent publication 188396;European patent publication 683172; International patent publication WO98/26783; International patent publication WO 98/27986; Internationalpatent publication WO 98/31702; European patent publication 903146; andInternational patent publications WO 99/41256 and WO 99/41257. As notedabove, the texts of all of these publications are incorporated byreference herein in their entireties.

[0530] Following are listed particular examples of GR antagonists thatmay be used in practicing the present invention. It is understood thatthe variables, e.g., “A”, “B”, “R₁”, “R₂”, etc., employed in the genericformula IA below have the meanings attributed to them only with respectto that particular formula.

[0531] For example, the GR antagonists may be of the followingstructural formula IA, including the pharmaceutically acceptable saltsthereof, as described in commonly assigned International patentapplication PCT/IB00/00366, filed Mar. 27, 2000:

[0532] an isomer thereof, a prodrug of said compound or isomer, or apharmaceutically acceptable salt of said compound, isomer or prodrug;

[0533] wherein m is 1 or 2;

[0534] - - - represents an optional bond;

[0535] A is selected from the group consisting of

[0536] D is CR₇, CR₇R₁₆, N, NR₇ or O;

[0537] E is C, CR₆ or N;

[0538] F is CR₄, CR₄R₅ or O;

[0539] G, H and I together with 2 carbon atoms from the A-ring or 2carbon atoms from the B-ring form a 5-membered heterocyclic ringcomprising one or more N, O or S atoms; provided that there is at mostone of O and S per ring; J, K, L and M together with 2 carbon atoms fromthe B-ring forms a 6-membered heterocyclic ring comprising 1 or more Natoms;

[0540] X is a) absent, b) —CH₂—, c) —CH(OH)— or d) —C(O)—;

[0541] R₁ is a) —H, b) —Z—CF₃, c) —(C₁-C₆)alkyl, d)—(C₂-C₆)alkenyl, e)—(C₂-C₆)alkynyl, f) —CHO, g) —CH=N—OR₁₂, h) —Z—C(O)OR₁₂, i)—Z—C(O)—NR₁₂R₁₃, j) —Z—C(O)—NR₁₂—Z-het, k) —Z—NR₁₂R₁₃, l) —Z—NR₁₂het, m)-Z-het, n) —Z—O—het, o) —Z-aryl′, p) —Z—O-aryl′, q) —CHOH-aryl′ or r)—C(O)-aryl′ wherein aryl′ in substituents o) to r) is substitutedindependently with 0, 1 or 2 of the following: —Z—OH, —Z—NR₁₂R₁₃,—Z—NR₁₂-het, —C(O)NR₁₂R₁₃, —C(O)O(C₁-C₆)alkyl, —C(O)OH, —C(O)-het,—NR₁₂—C(O)—(C₁-C₆)alkyl, —NR₁₂—C(O)—(C₂-C₆)alkenyl,—NR₁₂—C(O)—(C₂-C₆)alkynyl, —NR₁₂—C(O)—Z-het, —CN, —Z-het,—O—(C₁-C₃)alkyl-C(O)—N R₁₂R₁₃, —O—(C₁-C₃)alkyl-C(O)O(C₁-C₆)alkyl,—NR₁₂—Z—C(O)O(C₁-C₆)alkyl, —N(Z—C(O)O(C₁-C₆)alkyl)₂,—NR₁₂—Z—C(O)—NR₁₂R₁₃, —Z—NR₁₂—SO₂—R₁₃, —NR₁₂—SO₂-het, —C(O)H,—Z—NR₁₂—Z—O(C₁-C₆)alkyl, —Z—NR₁₂—Z—NR₁₂R₁₃, —Z—NR₁₂—(C₃-C₆)cycloalkyl,—Z—N(Z—O(C₁-C₆)alkyl)₂, —SO₂R₁₂, —SOR₁₂, —SR₁₂, —SO₂NR₁₂R₁₃,—O—C(O)—(C₁-C₄)alkyl, —O—SO₂—(C₁-C₄)alkyl, -halo or -CF₃;

[0542] Z for each occurrence is independently a) —(CO—C₆)alkyl, b)—(C₂-C₆)alkenyl or c) —(C₂-C₆)alkynyl;

[0543] R₂ is a) —H, b) -halo, c) —OH, d) —(C₁-C₆)alkyl substituted with0 or 1—OH, e) —NR₁₂R₁₃, f) —Z—C(O)O(C₁-C₆)alkyl, g) —Z—C(O)NR₁₂R₁₃, h)—O—(C₁-C₆)alkyl, i) —Z—O—C(O)—(C₁-C₆)alkyl, j)—Z—O—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃, k) —Z—O—(C₁-C₃)alkyl-C(O)—O(C₁-C₆)alkyl,l) —O—(C₂-C₆)alkenyl, m) —O—(C₂-C₆)alkynyl, n) —O—Z-het, o) —COOH, p)—C(OH)R₁₂R₁₃ or q) —Z—CN;

[0544] R₃ is a) —H, b) —(C₁-C₁₀)alkyl wherein 1 or 2 carbon atoms, otherthan the connecting carbon atom, may optionally be replaced with 1 or 2heteroatoms independently selected from S, O and N and wherein eachcarbon atom is substituted with 0, 1 or 2 R_(y), c)—(C₂-C₁₀)alkenylsubstituted with 0, 1 or 2 R_(y), d) —(C₂-C₁₀)alkynyl wherein 1 carbonatom, other than the connecting carbon atom, may optionally be replacedwith 1 oxygen atom and wherein each carbon atom is substituted with 0, 1or 2 R_(y), e) —CH═C═CH₂, f) —CN, g) —(C₃-C₆)cycloalkyl, h) —Z-aryl, i)—Z-het, j) —C(O)O(C₁-C₆)alkyl, k) —O(C₁-C₆)alkyl, l) —Z—S—R₁₂, m)—Z—S(O)—R₁₂, n) —Z—S(O)₂—R₁₂, o) —CF₃p) —NR₁₂O—(C₁-C₆)alkyl or q)—CH₂OR_(y);

[0545] provided that one of R₂ and R₃ is absent when there is a doublebond between CR₂R₃ (the 7 position) and the F moiety (the 8 position) ofthe C-ring;

[0546] R_(y) for each occurrence is independently a) —OH, b) -halo, c)—Z—CF₃, d) —Z—CF(C₁-C₃ alkyl)₂, e) —CN, f) —NR₁₂R₁₃, g)—(C₃-C₆)cycloalkyl, h) —(C₃-C₆)cycloalkenyl, i) —(CO—C₃)alkyl-aryl, j)-het or k) —N₃;

[0547] or R₂ and R₃ are taken together to form a) ═CHR₁₁, b) ═NOR₁₁, c)═11, d) ═N—NR₁₂, e) ═N—NR₁₂—C(O)—R₁₂, f) oxiranyl or g)1,3-dioxolan-4-yl;

[0548] R₄ and R₅ for each occurrence are independently a) —H, b) —CN, c)—(C₁-C₆)alkyl substituted with 0 to 3 halo, d) —(C₂-C₆)alkenylsubstituted with 0 to 3 halo, e) —(C₂-C₆)alkynyl substituted with 0 to 3halo, f) —O—(C₁-C₆)alkyl substituted with 0 to 3 halo, g)—O—(C₂-C₆)alkenyl substituted with 0 to 3 halo, h) —O—(C₂-C₆)alkynylsubstituted with 0 to 3 halo, i) halo, j) —OH, k) (C₃-C₆)cycloalkyl orl) (C₃-C₆)cycloalkenyl;

[0549] or R₄ and R₅ are taken together to form ═O;

[0550] R₆ is a) —H, b) —CN, c) —(C₁-C₆)alkyl substituted with 0 to 3halo, d) —(C₂-C₆)alkenyl substituted with 0 to 3 halo, e)—(C₂-C₆)alkynyl substituted with 0 to 3 halo or f) —OH;

[0551] R₇ and R₁₆ for each occurrence are independently a) —H, b) -halo,c) —CN, d) —(C₁-C₆)alkyl substituted with 0 to 3 halo, e)—(C₂-C₆)alkenyl substituted with 0 to 3 halo or f) —(C₂-C₆)alkynylsubstituted with 0 to 3 halo; provided that R₇ is other than —CN or-halo when D is NR₇;

[0552] or R₇ and R₁₆ are taken together to form ═O;

[0553] R₈, R₉, R₁₄ and R,₅ for each occurrence are independently a) —H,b) -halo, c) (C₁-C₆)alkyl substituted with 0 to 3 halo, d)—(C₂-C₆)alkenyl substituted with 0 to 3 halo, e) —(C₂-C₆)alkynylsubstituted with 0 to 3 halo, f) —CN, 9) —(C₃-C₆)cycloalkyl, h)—(C₃-C₆)cycloalkenyl, i) —OH, j) —O—(C₁-C₆)alkyl, k) —O—(C₁-C₆)alkenyl,l) —O—(C₁-C₆)alkynyl, m) —NR₁₂R₁₃, n) —C(O)OR₁₂ or o) —C(O)NR₁₂R₁₃;

[0554] or R₈ and R₉ are taken together on the C-ring to form ═O;provided that when m is 2, only one set of R₈ and R₉ are taken togetherto form ═O;

[0555] or R₁₄ and R₁₅ are taken together to form ═O; provided that whenR₁₄ and R₁₅ are taken together to form ═O, D is other than CR₇ and E isother than C;

[0556] R₁₀ is a) —(C₁-C₁₀)alkyl substituted with 0 to 3 substituentsindependently selected from -halo, —OH and —N₃, b) —(C₂-C₁₀)alkenylsubstituted with 0 to 3 substituents independently selected from -halo,—OH and —N₃, c) —(C₂-C₁₀)alkynyl substituted with 0 to 3 substituentsindependently selected from -halo, —OH and —N₃, d) -halo, e) —Z—CN, f)—OH, g) —Z-het, h) —Z—NR₁₂R₁₃, i) —Z—C(O)-het, j) —Z—C(O)—(C₁-C₆)alkyl,k) —Z—C(O)—NR₁₂R₁₃, l) —Z—C(O)—NR₁₂—Z—CN, m) —Z—C(O)—NR₁₂-Z-het, n)—Z—C(O)—NR₁₂—Z-aryl, o) —Z—C(O)—NR₁₂—Z—NR₁₂R₁₃, p)—Z—C(O)—NR₁₂—Z—O(C₁-C₆)alkyl, q) —(C₁-C₆)alkyl-C(O)OH, r)—Z—C(O)O(C₁-C₆)alkyl, s) —Z—O—(C₀-C₆)alkyl-het, t)—Z—O—(C₀-C₆)alkyl-aryl, u) —Z—O—(C₁-C₆)alkyl substituted with 0 to 2R_(x), v) —Z—O—(C₁-C₆)alkyl-CH(O), w) —Z—O—(C₁-C₆)alkyl-NR₁₂-het, x)—Z—O—Z-het-Z-het, y) —Z—O—Z-het-Z—NR₁₂R₃₃, z) —Z—O—Z-het-C(O)-het, a1)—Z—O—Z—C(O)-het, b1) —Z—O—Z—C(O)-het-het, c1) —Z—O—Z—C(O)—(C₁-C₆)alkyl,d1) —Z—O—Z—C(S)—NR₁₂R₁₃, e1) —Z—O—Z—C(O)—NR₁₂R₁₃, f1)—Z—O—Z—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃, g1) —Z—O—Z—C(O)—O(C₁-C₆)alkyl, h1)—Z—O—Z—C(O)—OH, i1) —Z—O—Z—C(O)—NR₁₂—O(C₁-C₆)alkyl, j1)—Z—O—Z—C(O)—NR₁₂—OH, k1) —Z—O—Z—C(O)—NR₁₂—Z—NR₁₂R₁₃, l1)—Z—O—Z—C(O)—NR₁₂—Z-het, m1) —Z—O—Z—C(O)—NR₁₂—SO₂—(C₁-C₆)alkyl, n1)—Z—O—Z—C(═NR₁₂)(NR₁₂R₁₃), o1) —Z—O—Z—C(═NOR₁₂)(NR₁₂R₁₃), p1)—Z—NR₁₂—C(O)—O—Z—NR₁₂R₁₃, q1) —Z—S—C(O)—NR₁₂R₁₃, r1)—Z—O—SO₂—(C₁-C₆)alkyl, s1) —Z—O—SO₂-aryl, t1) —Z—O—SO₂—NR₁₂R₁₃, u1)—Z—O—SO₂-CF₃, v1) —Z—NR₁₂C(O)OR₁₃ or w1) —Z—NR₁₂C(O)R₁₃;

[0557] or R₉ and R₁₀ are taken together on the moiety of formula A-5 toform a) ═O or b) ═NOR₁₂;

[0558] R₁₁ is a) —H, b) —(C₁-C₅)alkyl, c) —(C₃-C₆)cycloalkyl or d)—(C₀-C₃)alkyl-aryl;

[0559] R₁₂ and R₁₃ for each occurrence are each independently a) —H, b)—(C₁-C₆)alkyl wherein 1 or 2 carbon atoms, other than the connectingcarbon atom, may optionally be replaced with 1 or 2 heteroatomsindependently selected from S, O and N and wherein each carbon atom issubstituted with 0 to 6 halo, c) —(C₂-C₆)alkenyl substituted with 0 to 6halo or d) —(C₁-C₆)alkynyl wherein 1 carbon atom, other than theconnecting carbon atom, may optionally be replaced with 1 oxygen atomand wherein each carbon atom is substituted with 0 to 6 halo;

[0560] or R₁₂ and R₁₃ are taken together with N to form het;

[0561] or R₆ and R₁₄ or R₁₅ are taken together to form 1,3-dioxolanyl;

[0562] aryl is a) phenyl substituted with 0 to 3 R_(x), b) naphthylsubstituted with 0 to 3 R_(x) or c) biphenyl substituted with 0 to 3R_(x);

[0563] het is a 5- ,6- or 7-membered saturated, partially saturated orunsaturated ring containing from one (1) to three (3) heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur; and including any bicyclic group in which any of the aboveheterocyclic rings is fused to a benzene ring or another heterocycle;and the nitrogen may be in the oxidized state giving the N-oxide form;and substituted with 0 to 3 R_(x);

[0564] R_(x) for each occurrence is independently a) -halo, b) —OH, c)—(C₁-C₆)alkyl, d) —(C₂-C₆)alkenyl, e) —(C₂-C₆)alkynyl, f)—O(C₁—C₆)alkyl, g) —O(C₂-C₆)alkenyl, h) —O(C₂-C₆)alkynyl, i)—(C₀-C₆)alkyl-NR₁₂R₁₃, j) —C(O)—NR₁₂R₁₃, k) —Z—SO₂R₁₂, l) —Z—SOR₁₂, m)—Z—SR₁₂, n) —NR₁₂—SO₂R₁₃, o) —NR₁₂—C(O)—R₁₃, p) —NR₁₂—OR₁₃, q)—SO₂-NR₁₂R₁₃, r) —CN, s) —CF₃, t) —C(O)(C₁-C₆)alkyl, u) ═O, v)—Z—SO₂-phenyl or w) —Z—SO₂-het′;

[0565] aryl′ is phenyl, naphthyl or biphenyl;

[0566] het′ is a 5-, 6- or 7-membered saturated, partially saturated orunsaturated ring containing from one (1) to three (3) heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur; and including any bicyclic group in which any of the aboveheterocyclic rings is fused to a benzene ring or another heterocycle;

[0567] provided that:

[0568] 1) X—R₁ is other than hydrogen or methyl;

[0569] 2) when R₉ and R₁₀ are substituents on the A-ring, they are otherthan mono- or di-methoxy;

[0570] 3) when R₂ and R₃ are taken together to form ═CHR₁₁ or ═O whereinR₁₁ is —O(C₁-C₆)alkyl, then —X—R, is other than (C₁-C₄)alkyl;

[0571] 4) when R2 and R₃ taken together are C═O and R₉ is hydrogen onthe A-ring; or when R₂ is hydroxy, R₃ is hydrogen and R₉ is hydrogen onthe A-ring, then R₁₀ is other than —O—(C₁-C₆)alkyl or —O—CH₂-phenyl atthe 2-position of the A-ring;

[0572] 5) when X—R₁ is (C₁-C₄)alkyl, (C₂-C₄)alkenyl or (C₂-C₄)alkynyl,R₉ and R₁₀ are other than mono-hydroxy or ═O, including the diol formthereof, when taken together; and

[0573] 6) when X is absent, R₁ is other than a moiety containing aheteroatom independently selected from N, O or S directly attached tothe juncture of the B-ring and the C-ring.

[0574] The compounds of formula IA as described above, theirpharmaceutically acceptable salts, and methods of preparing suchcompounds and salts are disclosed in commonly International patentapplication PCT/IB00/00366, filed Mar. 27, 2000. This application,referred to above, is incorporated herein by reference in its entirety.

[0575] Specific GR antagonists useful in the practice of the presentinvention include, without limitation, the following compounds:

[0576] 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(4-pyridinylmethyl)-,[4bS-(4bα,7α, 8aβ)]-;

[0577] 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(2-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-;

[0578] 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(3-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-;

[0579] carbamic acid, [2-(dimethylamino)ethyl]-,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-2-phenanthrenylester,[4bS-(4bα,7α,8aβ)]-;

[0580] 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-pyrazinyl-,[4bS-(4bα,7α,8aβ)]-;

[0581] 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2-(1-propynyl)-7-(4-pyridinylmethoxy)-,[2R-(2α,4aα, 10aβ)];

[0582] 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2-(1-propynyl)-7-(2-pyridinylmethoxy)-,[2R-(2α4aα,10aβ)];

[0583] 2-phenanthrenecarbonitrile,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-,[4bS-(4bα,7α,8aβ)]-;

[0584] 2-phenanthrenecarboxamide, 4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(1-propynyl)-,[4bS-(4bα,7α,8aβ)]-;

[0585] 2-phenanthrenecarboxamide, 4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-propyl-,[4bS-(4bα,7α,8aβ)]-;

[0586] 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-propyl-N-(2-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-;

[0587] 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-7-(3-pyridinylmethoxy)-2-(3,3,3-trifluoropropyl)-,[2S-(2α,4aα, 10aβ)]-;

[0588] 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-7-[(2-methyl-3-pyridinyl)methoxy]-4a-(phenylmethyl)-2-(3,3,3-trifluoropropyl)-,[2S-(2α,4aα,10aβ)]-;

[0589] 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(3,3,3-trifluoropropyl)-,(4bS,7S,8aR);

[0590] 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-7-methyl-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-,(4bS,7R,8aR)-;

[0591] 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-7-methyl-4b-(phenylmethyl)-N-3-pyridinyl-,(4bS,7R,8aR)-;

[0592] 2-phenanthrenol, 1,2,3,4,4a,9,10,10a-octahydro-7-[(2-methyl-3-pyridinyl)methoxy]-4a-(phenylmethyl)-2-(trifluoromethyl)-,(2R,4aS, 10aR)-; and

[0593] 2-phenanthrenecarboxamide, 4b, 5, 6, 7, 8, 8a, 9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(trifluoromethyl)-,(4bS, 7R, 8aR)-.

[0594] Methods for making the GR antagonists described above aredisclosed in the above listed patents, applications and published patentapplications incorporated by reference herein.

[0595] Acid addition salts of the CRF antagonists and GR antagonistsemployed in the present invention can be prepared in a conventionalmanner by treating a solution or suspension of the corresponding freebase with one chemical equivalent of a pharmaceutically acceptable acid.Conventional concentration or crystallization techniques can be employedto isolate the salts. Illustrative of suitable acids are acetic, lactic,succinic, maleic, tartaric, citric, gluconic, ascorbic, benzoic,cinnamic, fumaric, sulfuric, phosphoric, hydrochloric, hydrobromic,hydroiodic, sulfamic, sulfonic acids such as methanesulfonic, benzenesulfonic, p-toluenesulfonic, and related acids.

[0596] The administration of the CRF antagonist and the GR antagonist,or pharmaceutically acceptable salts thereof, according to the presentinvention can be sequential in time or simultaneous, with thesimultaneous method being generally preferred. For sequentialadministration, the CRF antagonist and the GR antagonist can beadministered in any order. It is generally preferred that suchadministration be oral. It is even more preferred that theadministration be oral and simultaneous. However, if the subject beingtreated is unable to swallow, or oral absorption is otherwise impairedor undesirable, another route of administration such as suppositories,parenteral (such as subcutaneous, intravenous, intramuscular,intrasternal and infusion techniques), or topical administration will beappropriate. When the CRF antagonist and the GR antagonist areadministered sequentially, the administration of each can be by the samemethod or by different methods.

[0597] The pharmaceutical compositions of the present invention compriseamounts of a CRF antagonist alone or together with a GR antagonist. Oneaspect of the present invention provides compositions comprising amountsof a CRF antagonist and a GR antagonist which result in a therapeuticeffect. Of such compositions, compositions comprising a CRF antagonistas disclosed in EP 0773023 (which is described above) or apharmaceutically acceptable salt thereof, and a GR antagonist asdisclosed in International patent application PCT/IB00/00366, filed Mar.27, 2000 (which is described above) or a pharmaceutically acceptablesalt thereof are preferred. It is further preferred that thecompositions comprising the CRF antagonist and the GR antagonist beadministered in the presence of a pharmaceutically acceptable vehicle,carrier or diluent, in either single or multiple doses.

[0598] Suitable pharmaceutical vehicles, carriers and diluents includeinert solid diluents or fillers, sterile aqueous solutions, and variousorganic solvents. The pharmaceutical compositions formed by combiningthe active compound(s) and the pharmaceutically acceptable carriers arethen readily administered in a variety of dosage forms such as tablets,powders, lozenges, syrups, injectable solutions, and the like. Thesepharmaceutical compositions can, if desired, contain additionalingredients such as flavorings, binders, excipients, and the like. Thus,for purposes of oral administration, tablets containing variousexcipients such as sodium citrate, calcium carbonate, and calciumphosphate may be employed along with various disintegrants such asstarch, alginic acid, and certain complex silicates, together withbinding agents such as polyvinylpyrrolidone, sucrose, gelatin, andacacia. Additionally, lubricating agents such as magnesium stearate,sodium lauryl sulfate, and talc are often useful for tablettingpurposes. Solid compositions of a similar type can also be employed asfillers in soft and hard filled gelatin capsules. Preferred materialsfor this include lactose or milk sugar and high molecular weightpolyethylene glycols. When aqueous suspensions or elixirs are desiredfor oral administration, the active ingredient(s) therein may becombined with various sweetening or flavoring agents, coloring matter ordyes and, if desired, emulsifying or suspending agents, together withdiluents such as water, ethanol, propylene glycol, glycerin, andcombinations thereof.

[0599] For parenteral administration, solutions of the activecompound(s) in sesame or peanut oil, aqueous propylene glycol, or insterile aqueous solution can be employed. Such aqueous solutions shouldbe suitably buffered if necessary and the liquid diluent first renderedisotonic with sufficient saline or glucose. These particular aqueoussolutions are especially suitable for intravenous, intramuscular,subcutaneous, and intraperitoneal administration. The sterile aqueousmedia employed are all readily available by standard techniques known tothose skilled in the art.

[0600] For purposes of transdermal (e.g., topical) administration,dilute, sterile, aqueous or partially aqueous solutions (usually inabout 0.1% to 5% concentration), otherwise similar to the aboveparenteral solutions, are employed.

[0601] Methods of preparing various pharmaceutical compositions with acertain amount of active ingredient(s) are known, or will be apparent inlight of this disclosure, to those skilled in the art. For example, seeRemington's Pharmaceutical Sciences, Mack Publishing Company, Easton,Pa., 19th Edition (1995).

[0602] A therapeutically effective amount of an active ingredient meansan amount that ameliorates, attenuates, or eliminates one or moresymptoms of a particular disease or condition or prevents or delays theonset of one of more symptoms of a particular disease or condition.Amount(s) of the CRF antagonist alone or in combination with the GRantagonist necessary to achieve the desired therapeutic effect accordingto the present invention are within the skill of those who practice inthe art of having the benefit of the disclosure herein. SyndromeX-treating or preventing amount(s) of the CRF antagonist alone or incombination with the GR antagonist are preferred.

[0603] In general, the effective dosage for the CRF antagonist employedin the present invention will depend on the intended route ofadministration and factors such as the age and weight of the patient, asgenerally known to a physician. The dosage will also depend on theparticular condition to be treated and will generally range from about0.1 to about 300 mg/kg body weight of the patient per day, withadministration carried out in single or divided dosages.

[0604] In general, the effective dosage for the GR antagonist employedin the present invention will range from about 0.1 μg/kg of body weightto about 500 mg/kg of body weight, more particularly from about 1 μg/kgto about 250 mg/kg, and most particularly from about 2 μg/kg to about100 mg/kg. More preferably, the GR antagonist will be administered at anamount of about 0.1 mg/kg to about 500 mg/kg of body weight, and mostpreferably from about 0.1 mg/kg to about 50 mg/kg of body weight. Asrecognized by those skilled in the art, the particular quantity of theGR antagonist to be administered to a patient according to the presentinvention will depend upon a number of factors, including, withoutlimitation, the biological activity desired, the condition of thepatient, and tolerance for the drug.

[0605] The methods and compositions of the present invention haveutility in the treatment or prevention of Syndrome X in animals, such asdogs, cats, cows, horses, sheep, and humans. Particularly preferredanimals are mammals, including both males and females. As such, themethods and compositions of the present invention have utility in thetreatment or prevention of Syndrome X in companion animals, such as dogsand cats. The administration of the compositions of this invention maybe effected orally or parenterally. An amount of a composition of theinvention is administered such that an effective dose is received,usually a daily dose.

[0606] Conveniently, the medicaments can be carried in the drinkingwater such that a therapeutic dosage of the agent(s) is ingested withthe daily water supply. The agent(s) can be directly metered intodrinking water, preferably in the form of a liquid, water-solubleconcentrate, such as an aqeuous solution of a water-soluble salt.

[0607] Conveniently, the active ingredient(s) can also be added directlyto the companion animal's feed, as such, or in the form of an animalfeed supplement, also referred to as a premix or concentrate. A premixor concentrate of the therapeutic agent(s) in a carrier is more commonlyemployed for the inclusion of the agent in the feed. Suitable carriersare liquid or solid, as desired, such as water, various meals such asalfalfa meal, soybean meal, cottonseed oil meal, linseed oil meal,corncob meal and corn meal, molasses, urea, bone meal, and variousmineral mixes. A particularly effective carrier is the respective animalfeed itself, i.e., a small portion of such feed. The carrier facilitatesuniform distribution of the active material(s) in the finished feed withwhich the premix is blended. It is important that the compound(s) bethoroughly blended into the premix and, subsequently, the feed. In thisrespect, the agent(s) may be dispersed or dissolved in a suitable oilyvehicle such as soybean oil, corn oil, cottonseed oil, and the like, orin a volatile organic solvent and then blended with the carrier. It willbe appreciated that the proportions of active material(s) in theconcentrate are capable of wide variation since the amount of agent(s)in the finished feed may be adjusted by blending the appropriateproportion of premix with the feed to obtain a desired level of thetherapeutic agent(s).

[0608] High potency concentrates may be blended by the feed manufacturerwith a proteinaceous carrier such as soybean oil meal and other meals,as described above, to produce concentrated supplements which aresuitable for direct feeding to animals. In such instances, the animalsare permitted to consume the usual diet. Alternatively, suchconcentrated supplements may be added directly to the feed to produce anutritionally balanced, finished feed containing a therapeuticallyeffective amount of the compound(s) according to the present invention.The mixtures are thoroughly blended by standard procedures, such as in atwin shell blender, to insure homogeneity.

[0609] If the supplement is used as a top dressing for the feed, itlikewise helps to insure uniformity of distribution of the activeingredient(s) across the top of the dressed feed.

[0610] For veterinary uses, both paste and pellet formulations may alsobe conveniently employed. Paste formulations can be prepared readily bydispersing the active compound(s) in a pharmaceutically acceptable oilsuch as peanut oil, sesame oil, corn oil, and the like. Similarly,pellets containing an effective amount of the compound(s) of the presentinvention can be prepared by admixing the compound(s) of the inventionwith a suitable diluent such as carbowax, carnuba wax, and the like, anda lubricant, such as magnesium or calcium stearate, can be employed toimprove the pelleting process.

[0611] Since one aspect of the present invention relates to thetreatment or prevention of Syndrome X with a combination of activeingredients which may be administered separately, the invention alsorelates to combining separate pharmaceutical compositions in kit form. Akit, according to this invention, comprises two separate pharmaceuticalcompositions: a first unit dosage form, comprising a therapeuticallyeffective amount of a CRF antagonist and a pharmaceutically acceptablevehicle, carrier or diluent, and a second unit dosage form comprising atherapeutically effective amount of a GR antagonist and apharmaceutically acceptable vehicle, carrier or diluent. The kit furthercomprises a container. The container is used to contain the separatecompositions and may comprise, for example, a divided bottle or adivided foil packet; however, the separate compositions may also becontained within a single, undivided container. Normally, the kit willalso include directions for the administration of the separatecomponents. The kit form is particularly advantageous when the separatecomponents are preferably administered in different dosage forms (e.g.,oral and parenteral), are administered at different dosage levels, orwhen titration of the individual components of the combination isdesired by the prescribing physician.

[0612] An example of such a kit is a so-called blister pack. Blisterpacks are well known in the packaging industry and are being used widelyfor the packaging of pharmaceutical unit dosage forms (tablets, capsulesand the like). Blister packs generally consist of a sheet of relativelyrigid material covered with a foil of a preferably transparent plasticmaterial. During the packaging process recesses are formed in theplastic foil. The recesses generally conform to the size and shape ofthe tablets or capsules to be contained therein. Next, the tablets orcapsules are placed in the recesses and the sheet of relatively rigidmaterial is sealed against the plastic foil at the face of the foilwhich is opposite from the direction in which the recesses were formed.As a result, the tablets or capsules are sealed in the recesses betweenthe plastic foil and the sheet. Preferably, the strength of the sheet issuch that the tablets or capsules may be removed from the blister packby the application of manual pressure on the recesses whereby an openingis formed in the sheet at the place of the recess. The tablet or capsulecan then be removed through the formed opening.

[0613] It is further desirable to provide a memory aid on the pack,e.g., in the form of numbers or similar indicia next to the tablets orcapsules whereby the indicia correspond with the days of the regimenwhich the dosage form so specified is to be ingested. An additionalexample of such a memory aid is a calendar printed on the pack, e.g., asfollows “First Week, Monday, Tuesday, . . . etc . . . Second Week,Monday, Tuesday, . . . ” etc. Other variations will be readily apparent.A “daily dose” can be a single tablet or capsule or multiple tablets orcapsules to be ingested on a given day. Also, a daily dose of a CRFantagonist can consist of one tablet or capsule while a daily dose of aGR antagonist can consist of multiple tablets or capsules, or viceversa. The memory aid should reflect this.

[0614] In another specific embodiment of the invention, a pack designedto dispense the daily doses one at a time in the order of their intendeduse is provided. Preferably, the pack is equipped with a memory aid, soas to further facilitate compliance with the dosage regimen. An exampleof such a memory aid is a mechanical counter which indicates the numberof daily doses to be dispensed. Another example of such a memory aid isa battery-powered micro-chip memory coupled with a liquid crystalreadout, or audible reminder signal which, for example, reads out thedate that the last daily dose has been taken and/or reminds the patientwhen the next dose is to be taken.

[0615] The following references disclose animal models, such as the JCR:LA-corpulent (cp) rat or the obese Zucker rat, that may be used todetermine the Syndrome X-treating activity of the compound(s) employedto practice the present invention: J. C. Russell et al., Metabolism,Vol. 48, No. 6 (June), 1999: pp 701-706; Diabetes 46:1958-1964, 1997.

[0616] Methods that may be used to determine CRF antagonist activity ofthe compounds employed to practice the present invention are asdescribed in, e.g., Wynn et al., Endocrinology, 116:1653-1659 (1985),and Grigoriadis et al., Peptides, 10:179-188 (1989). Methods that can beused to determine the CRF binding protein inhibiting activity ofcompounds employed to practice the present invention are described inBrain Research, (1997), 745(1,2), 248-256. These methods determine thebinding affinity of a test compound for a CRF receptor, which is highlyrelated to its expected activity as a CRF antagonist.

[0617] Methods that may be used to determine GR antagonist activity ofthe compounds employed to practice the present invention are describedbelow and in commonly assigned International patent applicationPCT/IB00/00366, filed Mar. 27, 2000, which is hereby incorporated byreference herein. These methods determine the binding affinity of a testcompound for a GRA receptor, which is highly related to its expectedactivity as a GR antagonist.

[0618] The following is a description of an assay for the identificationof glucocorticoid receptor antagonists/agonists: HeLa cells (AmericanType Culture Collection (ATCC), Rockville, Md.) containing endogenoushuman glucocorticoid receptors are transfected with a3×pLuxF47-GRE-luciferase plasmid generated by standard procedures and aplasmid conferring neomycin resistance. pLuxF47-GRE was constructed byannealing oligonucleotides 23907-26A and 23907-26B and ligating into theBg I II and Eag I sites of pLuxF47. Novel glucocorticoid responsive celllines are generated and characterized. One such cell line designatedHeLa-GRE9 is used for determining the activity of compounds at theglucocorticoid receptor. Cells are maintained in charcoal-stripped serumand transferred to 96-well microtiter plates one day prior to treatmentwith various concentrations (10⁻¹² to 10⁻⁵) of test compounds in theabsence and presence of known glucocorticoid receptor agonists (i.e.,dexamethasone, hydrocortisone) for up to 24 hours. Treatments areperformed in triplicate. Cell lysates are prepared and luciferaseactivity is determined using a luminometer. Agonist activity is assessedby comparing the luciferase activity from cells treated with testcompound to cells treated with the agonist dexamethasone. Antagonistactivity is assessed by comparing the luciferase activity of an EC₅₀concentration of dexamethasone in the absence and presence of testcompound. The EC₅₀ (concentration that produced 50% of the maximalresponse) for dexamethasone is calculated from dose response curves.

[0619] The following is a description of an assay for determining thecompetitive inhibition binding of the Human Type II Glucocorticoidreceptor expressed in Sf9 cells:

[0620] Binding protocol: Compounds are tested in a binding displacementassay using human glucocorticoid receptor expressed in Sf9 cells with³H-dexamethasone as the ligand. Human glucorticoid receptor is expressedin Sf9 cells as described in Mol. Endocrinology 4: 209, 1990. Pelletscontaining Sf9 cells expressing the human GR receptor from 1 L vats arelysed with 40 ul of 20 mM AEBSF stock (Calbiochem, LaJolla, Calif.)containing 50 mg/ml leupeptin and 40 ml of homogenization buffer isadded. The assay is carried out in 96-well polypropylene plates in afinal volume of 130 ul containing 200 ug Sf9 lysate protein, 6.9 nM³H-dexamethasone (Amersham, Arlington Heights, Ill.) in presence of testcompounds, test compound vehicle (for total counts) or excessdexamethasone (7 uM non-radioactive, to determine non-specific binding)in an appropriate volume of assay buffer. All compounds are tested at 6concentrations in duplicate (concentration range 0.1-30 nM or 3-1000nM). Test compounds are diluted from a 25 mM stock in 100% DMSO with70%EtOH and added in a volume of 2 μl. Once all additions are made theplates are shaken, sealed with sealing tape and incubated at 4° C.overnight.

[0621] After the overnight incubation, unbound counts are removed withdextran coated charcoal as follows: 75 μl of dextran coated charcoal(5.0 g activated charcoal, 0.5 g dextran adjusted to volume of 100 mlwith assay buffer) is added, plates are shaken and incubated for fiveminutes at 4° C. Plates are then centrifuged in a refrigerated benchtopcentrifuge at top speed for 15 minutes. 100 μl of the supernatant fromeach well is placed into a 96-well PET plate with 200 μl ofscintillation cocktail and counted on a beta counter (1450MicroBetaTrilux, from Wallac, Turku, Finland).

[0622] Data analysis: After subtracting non-specific binding, countsbound are expressed as % of total counts. The concentration response fortest compounds are fitted to a sigmoidal curve to determine the IC₅₀(concentration of compound that displaces 50% of the bound counts).

[0623] Reagents: Assay Buffer: 2.0 ml 1M Tris (pH 7.4), 0.2 ml 0.5 mMEDTA (pH 8.0), 77.1 mg DTT, 0.243 g sodium molybdate in a volume of 100ml water; Homogenization buffer: 2.0 ml 0.5 M K₂HPO₄ (pH 7.6), 20 μl 0.5M EDTA (pH 8.0), 77.1 mg DTT, 0.486 g sodium molybdate in a volume of100 ml water.

[0624] The following is a description of an assay for determiningreceptor selectivity: T47D cells (American Type Culture Collection(ATCC), Rockville, Md.) containing endogenous human progesterone andmineralocorticoid receptors are transiently transfected with a3×pLuxF47-GRE-luciferase using Lipofectamine Plus (GIBCO-DRL,Gaithersburg, Md.). Twenty-four hours post-transfection cells aremaintained in charcoal-stripped serum and transferred to 96-wellmicrotiter plates. The next day cells are treated with variousconcentrations (10⁻¹² to 10⁻⁵) of test compounds in the absence andpresence of a known progesterone receptor agonist (progesterone) and aknown mineralocorticoid receptor agonist (aldosterone) for up to 24hours. Treatments are performed in triplicate. Cell lysates are preparedand luciferase activity is determined using a luminometer. Agonistactivity is assessed by comparing the luciferase activity from cellstreated with compound alone to cells treated with either the agonistprogesterone or aldosterone. Antagonist activity is assessed bycomparing the luciferase activity of an EC₅₀ concentration ofprogesterone or aldosterone in the absence and presence of compound. TheEC₅₀ (concentration that produced 50% of maximal response) forprogesterone and aldosterone is calculated from dose response curves.

[0625] The following is a description of an assay for determininganti-diabetes and anti-obesity activity. The obese, diabetic ob/ob mouseis used to assess the anti-diabetes and anti-obesity activity of thecompounds. Six to 10 week old ob/ob male mice (Jackson Labs, Bar Harbor,Me.) are dosed with test compound(s) for 2 to 10 days. Plasma glucoselevels are determined by measuring glucose from samples obtained byorbital bleeding. Glucose is quantitated using an Abbott Autoanalyzer(Abbott, Inc., Abbott Park, Ill.). Food intake is monitored on a dailybasis by differential weighing.

[0626] The following is a description of an assay for determining theability of a compound to inhibit glucocorticoid agonist induction ofliver tyrosine amino transferase (TAT) activity in conscious rats:

[0627] Animals: Male Sprague Dawley rats (from Charles River,Wilimington Mass.) (adrenal-intact or adrenalectomized at least one weekprior to the screen) b.w. 90 g are used. The rats are housed understandard conditions for 7-10 d prior to use in the screen.

[0628] Experimental protocol: Rats (usually 3 per treatment group) aredosed with test compound, vehicle or positive control (RU486) eitheri.p., p.o., s.c. or i.v. (tail vein). The dosing vehicle for the testcompounds is typically one of the following: 100% PEG 400, 0.25% methylcellulose in water, 70% ethanol or 0.1 N HCl and the compounds aretested at doses ranging from 10 to 125 mg/kg. The compounds are dosed ina volume of 1.0 ml/ 100 g body weight (for p.o.) or 0.1 ml/100 g bodyweight for other routes of administration . Ten minutes after theadministration of the test compound, the rats are injected withdexamethasone (0.03 mg/kg i.p. in a volume of 0.1 ml/ 100 g) or vehicle.To prepare the dexamethasone dosing solution, dexamethasone (from Sigma,St. Louis, Mo.) is dissolved in 100% ethanol and diluted with water(final: 10% ethanol:90% water, vol:vol). Groups treated withvehicle-vehicle, vehicle-dexamethasone, and Ru486-dexamethasone areincluded in each screen. The compounds are tested vs. dexamethasoneonly. Three hours after the injection of dexamethasone the rats aresacrificed by decapitation. A sample of liver (0.3 g) is excised andplaced in 2.7 ml of ice cold buffer and homogenized with a polytron. Toobtain cytosol the liver homogenate is centrifuged at 105,000 g for 60min and the supernatant is stored at −80° C. until analysis. TAT isassayed on 100 ul of a 1:20 dilution of the 105,000 g supernatant usingthe methods of D. K. Granner and G. M. Tomkins, “TyrosineAminotransferase (Rat Liver),” Methods in Enzymology, 17A: 633-637(1970) and a reaction time of 8-10 minutes. TAT activity is expressed asumol product/min/g liver.

[0629] Interpretation: Treatment data are analyzed by using analysis ofvariance (ANOVA) with protected least significant difference (PLSD)post-hoc analysis. Compounds are considered active in this test if theTAT activity in the group pretreated with compound prior todexamethasone administration is significantly (P<0.05) decreasedrelative to the TAT activity in the vehicle-dexamethasone treated group.

1. A method of treating or preventing Syndrome X in an animal whichcomprises administering to said animal an amount of a corticotropinreleasing factor antagonist.
 2. The method of claim 1 wherein atherapeutically effective amount of a corticotropin releasing factorantagonist is administered.
 3. The method of claim 2 wherein thecorticotropin releasing factor antagonist is a compound of formula

and the pharmaceutically acceptable acid addition salts thereof, whereinA is NR₁R₂, CR₁R₂R₁₁, or C(═CR₁R₁₂)R₂, NHCR₁R₂R₁₁, OCR₁R₂R₁₁, SCR₁R₂R₁₁,NHNR₁R₂, CR₂R₁₁NHR₁, CR₂R₁₁OR₁, CR₂R₁₁SR₁ or C(O)R₂; R₁ is hydrogen, orC₁-C₆ alkyl which may be substituted by one or two substituents R₆independently selected from the group consisting of hydroxy, fluoro,chloro, bromo, iodo, C₁-C₆ alkoxy, O—C(O)—(C₁-C₆ alkyl), O—C(O)—N(C₁-C₄alkyl)(C₁-C₂ alkyl); amino, NH(C₁-C₄ alkyl), S(C₁-C₆ alkyl),OC(O)NH(C₁-C₄ alkyl), N(C₁-C₂ alkyl)C(O)(C₁-C₄ alkyl), NHC(O)(C₁-C₄alkyl), COOH, CO(C₁-C₄ alkyl), C(O)NH(C₁-C₄ alkyl), C(O)N(C₁-C₄alkyl)(C₁-C₂ alkyl), SH, CN, NO₂, SO(C₁-C₄ alkyl); SO₂(C₁-C₄ alkyl),SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), and said C₁-C₆ alkylmay have one or two double or triple bonds; R₂ is C₁-C₁₂ alkyl, aryl or(C₁-C₁₀ alkylene)aryl wherein said aryl is phenyl, naphthyl, thienyl,benzothienyl, pyridyl, quinolyl, pyrazinolyl, pyrimidyl, imidazolyl,furanyl, benzofuranyl, benzothiazolyl, isothiazolyl, benzisothiazolyl,thiazolyl, isoxazolyl, benzisoxazolyl, benzimidazolyl, triazolyl,pyrazolyl, pyrrolyl, indolyl, azaindolyl, oxazolyl, or benzoxazolyl; 3-to 8-membered cycloalkyl or (C₁-C₆ alkylene) cycloalkyl, wherein saidcycloalkyl may have one or two of O, S or N—Z, wherein Z is hydrogen,substituted, independently, for one or two carbons of said cycloalkyl,C₁-C₄ alkyl, benzyl or C₁-C₄ alkanoyl, wherein R² may be substitutedindependently by from one to three of chloro, fluoro, or C₁-C₄ alkyl, orone of hydroxy, bromo, iodo, C₁-C₆ alkoxy, OC(O)(C₁-C₆ alkyl),O—C—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), S(C₁-C₆ alkyl), NH₂, NH(C₁-C₂ alkyl),N(C₁-C₄ alkyl) C(O)(C₁-C₄ alkyl), NHC(O)(C₁-C₄ alkyl), COOH, C(O)O(C₁-C₄alkyl), C(O)NH(C₁-C₄ alkyl), C(O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SH, CN,NO₂, SO(C₁-C₄ alkyl), SO₂(C₁-C₄ alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl), and wherein said C₁-C₁₂ alkyl or C₁-C₁₀ alkylenemay have one to three double or triple bonds; or NR₁R₂ or CR₁R₂R₁₁ mayform a 4- to 8-membered ring optionally having one or two double bondsor one or two of O, S or N—Z wherein Z is hydrogen, C₁-C₄ alkyl, benzyl,or C₁-C₄ alkanoyl; R₃ is hydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo,iodo, hydroxy, amino, O(C₁-C₆ alkyl), NH(C₁-C₆ alkyl), N(C₁-C₄alkyl)(C₁-C₂ alkyl), SH, S(C₁-C₄ alkyl), SO(C₁-C₄ alkyl), or SO₂(C₁-C₄alkyl), wherein said C₁-C₄ alkyl and C₁-C₆ alkyl may have one or twodouble or triple bonds and may be substituted by from 1 to 3 R₇substituents independently selected from the group consisting ofhydroxy, amino, C₁-C₃ alkoxy, dimethylamino, diethylamino, methylamino,ethylamino, NHC(O)CH₃, fluoro, chloro or C₁-C₃ thioalkyl; R₄ ishydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo, C₁-C₆ alkoxy, amino,NH(C₁-C₆ alkyl), N(C₁-C₆ alkyl) (C₁-C₂ alkyl), SO_(n)(C₁-C₆ alkyl),wherein n is 0, 1 or 2, cyano, hydroxy, carboxy, or amido, wherein saidC₁-C₆ alkyls may be substituted by one to three of hydroxy, amino,carboxy, amido, NHC(O)(C₁-C₄ alkyl), NH(C₁-C₄ alkyl), N(C₁-C₄alkyl)(C₁-C₂ alkyl), C(O)O(C₁-C₄ alkyl), C₁-C₃ alkoxy, C₁-C₃ thioalkyl,fluoro, bromo, chloro, iodo, cyano or nitro; R₅ is phenyl, naphthyl,thienyl, benzothienyl, pyridyl, quinolyl, pyrazinolyl, pyrimidyl,imidazolyl, furanyl, benzofuranyl, benzothiazolyl, isothiazolyl,benzoisothiazolyl, thiazolyl, isoxazolyl, benzisoxazolyl,benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridylbenzoxazolyl, oxazolyl, pyrrolidinyl, thiazolidinyl, piperazinyl,piperidinyl, or tetrazolyl, wherein each one of the above groups may besubstituted independently by from one to three of fluoro, chloro, bromo,formyl, C₁-C₆ alkyl, C₁-C₆ alkoxy or trifluoromethyl, or one of hydroxy,iodo, cyano, nitro, amino, cyclopropyl, NH(C₁-C₄ alkyl), N(C₁-C₄alkyl)(C₁-C₂ alkyl), COO(C₁-C₄ alkyl), CO(C₁-C₄ alkyl), SO₂NH(C₁-C₄alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SO₂NH₂, NHSO₂(C₁-C₄ alkyl),S(C₁-C₆ alkyl), SO₂(C₁-C₆ alkyl), wherein said C₁-C₄ alkyl and C₁-C₆alkyl may have one double or triple bond and may be substituted by oneor two of fluoro, chloro, hydroxy, amino, methylamino, dimethylamino oracetyl; with the proviso that R₅ is not unsubstituted phenyl; R₁₁ ishydrogen, hydroxy, fluoro, chloro, COO(C₁-C₂ alkyl), cyano, or CO(C₁-C₂alkyl); and R₁₂ is hydrogen or C₁-C₄ alkyl; (a) A is not straight chainC₁-C₁₂ alkyl; (b) when R₃is hydrogen, A is benzyl or phenethyl, and R₄is fluoro, chloro, bromo or iodo, then R5 is not 5′-deoxy-ribofuranosylor 5′-amino-5′-deoxy-ribofuranosyl; and (c) when R⁵ is phenyl, saidphenyl is substituted by two or three substituents.
 4. The method ofclaim 2 wherein the corticotropin releasing factor antagonist is acompound of formula

and the pharmaceutically acceptable acid addition salts thereof, whereinB is NR₁R₂, CR₁R₂R₁₁, C(═CR₂R₁₂)R₁, NHR₁R₂R₁₁, OCR₁R₂R₁₁,SCR₁R₂R₁₁NHNR₁R₂, CR₂R₁₁NHR₁, CR₂R₁₁OR₁, CR₂R₁₁SR₁ or C(O)R₂; R₁ ishydrogen, or C₁-C₆ alkyl which may be substituted by one or twosubstituents R₇ independently selected from the group consisting ofhydroxy, fluoro, chloro, bromo, iodo, C₁-C₈ alkoxy, O—C(═O)—(C₁-C₆alkyl), O—C(═O)NH(C₁-C₄ alkyl), O—C(═O)-N(C₁-C₄ alkyl)(C₁-C₂ alkyl),amino, NH(C₁-C₄ alkyl), N(C₁-C₂ alkyl)(C₁-C₄ alkyl), S(C₁-C₆ alkyl),N(C₁-C₄alkyl)C(═O)(C₁-C₄ alkyl), NH(C₁-C₄ alkyl), COOH, C(═O)O(C₁-C₄alkyl), C(═O)NH(C₁-C₄ alkyl), C(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SH, CN,NO₂, SO(C₁-C₄ alkyl), SO₂(C₁-C₄ alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl), and said C₁-C₆ alkyl may contain one or two doubleor triple bonds; R₂ is C₁-C₁₂ alkyl, aryl or (C₁-C₁₀ alkylene)arylwherein said aryl is phenyl, naphthyl, thienyl, benzothienyl, pyridyl,quinolyl, pyrazinyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl,benzothiazolyl, isothiazolyl, benzisothiazolyl, thiazolyl, isoxazolyl,benzisoxazolyl, benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl,pyrrolopyridyl, oxazolyl, or benzoxazolyl; 3- to 8-membered cycloalkylor (C₁-C₆ alkylene) cycloalkyl, wherein said cycloalkyl may contain oneor two of O, S or N—Z wherein Z is hydrogen, C₁-C₄ alkyl, benzyl orC₁-C₄ alkanoyl, wherein R₂ may be substituted independently by from oneto three of chloro, fluoro, or C₁-C₄ alkyl, or one of hydroxy, bromo,iodo, C₁-C₆ alkoxy, O—C(═O)—(C₁-C₆ alkyl), O—C—N(C₁-C₄ alkyl)(C₁-C₂alkyl), S(C₁-C₆ alkyl), NH₂, NH(C₁-C₂ alkyl), N(C₁-C₂ alkyl) (C₁-C₄alkyl), N(C₁-C₄)-C(═O)(C₁-C₄ alkyl), NHC(═O)(C₁-C₄), COOH, C(═O)O(C₁-C₄alkyl), C(═O)NH(C₁-C₄ alkyl), C(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SH, CN,NO₂, SO(C₁-C₄ alkyl), SO₂(C₁-C₄ alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl), and wherein said C₁-C₁₂ alkyl or C₁-C₁₀ alkylenemay contain one to three double or triple bonds; or NR₁R₂ or CR₁R₂R₁₁may form a saturated 3- to 8membered carbocyclic ring of which the 5- to8-membered ring contain one or two double bonds or one or two of O, S orN—Z wherein Z is hydrogen, C₁-C₄ alkyl, benzyl or C₁-C₄ alkanoyl; R₃ ishydrogen, C₁-C₆ alkyl, fluoro, chloro, bromo, iodo, hydroxy, amino,O(C₁-C₆ alkyl), NH(C₁-C₆ alkyl), N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SH,S(C₁-C₄ alkyl), SO(C₁-C₄ alkyl), or SO₂(C₁-C₄ alkyl), wherein said C₁-C₄alkyl and C₁-C₆ alkyl may contain from one or two double or triple bondsand may be substituted by from 1 to 3 substituents R₈ independentlyselected from the group consisting of hydroxy, amino, C₁-C₃ alkoxy,dimethylamino, diethylamino, methylamino, ethylamino, NHCH₃, fluoro,chloro or C₁-C₃ thioalkyl; R₄ and R6 are each independently hydrogen,C₁-C₆ alkyl, fluoro, chloro, bromo, iodo, C₁-C₆ alkoxy, amino, NH(C₁-C₆alkyl), N(C₁-C₆ alkyl)(C₁-C₂ alkyl), SO_(n)(C₁-C₆ alkyl), wherein n is0, 1 or 2, cyano, hydroxy, carboxy, or amido, wherein said C₁-C₆ alkylsmay be substituted by one to three of hydroxy, amino, carboxy, amido,NHC(═O)(C₁-C₄ alkyl), NH(C₁-C₄ alkyl), N(C₁-C₄ alkyl)(C₁-C₂ alkyl),C(═O)O(C₁-C₄ alkyl), C₁-C₃ alkoxy, C₁-C₃ thioalkyl, fluoro, bromo,chloro, iodo, cyano or nitro; R₅ is phenyl, naphthyl, thienyl,benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl,furanyl, benzofuranyl, benzothiazolyl, isothiazolyl, benzisothiazolyl,thiazolyl, isoxazolyl, benzisoxazolyl, benzimidazolyl, triazolyl,pyrazolyl, pyrrolyl, indolyl, azaindolyl, benzoxazolyl, oxazolyl,pyrrolidinyl, thiazolidinyl, morpholinyl, piperidinyl, piperazinyl,tetrazolyl, or 3- to 8-membered cycloalkyl or 9- to 12-memberedbicycloalkyl, optionally containing one to three of O, S or N—Z whereinZ is hydrogen, C₁-C₄ alkyl, C₁-C₄ alkanoyl, phenyl or phenylmethyl,wherein each one of the above groups may be substituted independently byfrom one to four of fluoro, chloro, C₁-C₆ alkyl, C₁-C₆ alkoxy ortrifluoromethyl, or one of bromo, iodo, cyano, nitro, amino, NH(C₁-C₄alkyl), N(C₁-C₄)(C₁-C₂ alkyl), COO(C₁-C₄ alkyl), CO(C₁-C₄ alkyl),SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SO₂NH₂, NHSO₂(C₁-C₄alkyl), S(C₁-C₆ alkyl), SO₂(C₁-C₆ alkyl), wherein said C₁-C₄ alkyl andC₁-C₆ alkyl may be substituted by one or two of fluoro, chloro, hydroxy,amino, methylamino, dimethylamino or acetyl; with the proviso that R₅ isnot unsubstituted phenyl; R₁₁ is hydrogen, hydroxy, fluoro, chloro,COO(C₁-C₂ alkyl), cyano, or CO(C₁-C₂ alkyl); and R₁₂ is hydrogen orC₁-C₄ alkyl; with the proviso that (1) when R₅ is 4-bromophenyl, R₃ ishydrogen, and R₄ and R₆ are methyl, then B is not methylamino or ethyl,and (2) when R5 is 4-bromophenyl, and R₃, R₄ and R₆ are methyl, then Bis not 2-hydroxyethylamino.
 5. The method of claim 2 wherein thecorticotropin releasing factor antagonist is a compound of formula

wherein A is CR₇ or N; B is NR₁R₂, CR₁R₂R₁₁, C(═CR₂R₁₂)R₁, NHCHR₁R₂,OCHR₁R₂, SCHR₁R₂, CHR₂OR₁₂, CHR₂SR₁₂, C(S)R₂ or C(O)R₂; G is oxygen,sulfur, NH, NH₃, hydrogen, methoxy, ethoxy, trifluoromethoxy, methyl,ethyl, thiomethoxy, NH₂, NHCH₃, N(CH₃)₂ or trifluromethyl; Y is CH or N;Z is NH, O, S, N (C₁-C₂ alkyl), or CR₁₃R₁₄, wherein R₁₃ and R₁₄ are eachindependently hydrogen, trifluoromethyl, or C₁-C₄ alkyl, or one of R₁₃and R₁₄ may be cyano, chloro, bromo, iodo, fluoro, hydroxy, O(C₁-C₂alkyl), amino, NH(C₁-C₂ alkyl), or CR₁₃R₁₄ may be C═O or cyclopropyl; R₁is C₁-C₆ alkyl which may be substituted by one or two substituents R₈independently selected from the group consisting of hydroxy, fluoro,chloro, bromo, iodo, C₁-C₄ alkoxy, O—CO—(C₁-C₄ alkyl), O—CO—NH(C₁-C₄alkyl), O—CO—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), NH(C₁-C₄ alkyl), N(C₁-C₂alkyl)(C₁-C₄ alkyl), S(C₁-C₄ alkyl), N(C₁-C₄alkyl)CO(C₁-C₄ alkyl),NHCO(C₁-C₄ alkyl), COO(C₁-C₄ alkyl), CONH(C₁-C₄ alkyl), CON(C₁-C₄alkyl)(C₁-C₂ alkyl), S(C₁-C₄ alkyl), CN, NO₂, SO(C₁-C₄ alkyl), SO₂(C₁-C₄alkyl), and said C₁-C₆ alkyl or C₁-C₄ alkyl may contain one double ortriple bond; R₂ is C₁-C₁₂ alkyl, aryl or (C₁-C₄ alkylene)aryl whereinsaid aryl is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, pyrimidyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, indolyl,or benzoxazolyl; 3- to 8-membered cycloalkyl or (C₁-C₆alkylene)cycloalkyl, wherein said cycloalkyl may contain one or two ofO, S or N—R₉ wherein R₉ is hydrogen, or C₁-C₄ alkyl, wherein the abovedefined R₂ may be substituted independently by from one to three ofchloro, fluoro, or C₁-C₄ alkyl, or one of bromo, iodo, C₁-C₆ alkoxy,O—CO—(C₁-C₆ alkyl), O—CO—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), S(C₁-C₆ alkyl),CN, NO₂, SO(C₁-C₄ alkyl), or SO₂(C₁-C₄ alkyl), and wherein said C₁-C₁₂alkyl or C₁-C₄ alkylene may contain one double or triple bond; or NR₁R₂or CR₁R₂R₁₁ may form a saturated 5- to 8-membered carbocyclic ring whichmay contain one or two double bonds or one or two of O or S; R₃ ismethyl, ethyl, fluoro, chloro, bromo, iodo, cyano, methoxy, OCF₃,methylthio, methylsulfonyl, CH₂OH or CH₂OCH₃; R₄ is hydrogen, C₁-C₄alkyl, fluoro, chloro, bromo, iodo, C₁-C₄ alkoxy, amino, nitro, NH(C₁-C₄alkyl), N(C₁-C₄ alkyl)(C₁-C₂ alkyl), SO_(n)(C₁-C₄ alkyl), wherein n is0, 1 or 2, cyano, hydroxy, CO(C₁-C₄ alkyl), CHO, or COO(C₁-C₄ alkyl),wherein said C₁-C₄ alkyl may contain one or two double or triple bondsand may be substituted by one or two of hydroxy, amino, carboxy,NHCOCH₃, NH(C₁-C₂ alkyl), N(C₁-C₂ alkyl)₂, COO(C₁-C₄ alkyl), CO(C₁-C₄alkyl), C₁-C₃ alkoxy, C₁-C₃ thioalkyl, fluoro, chloro, cyano or nitro;R₅ is phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, pyrimidyl, furanyl, benzofuranyl, benzothiazolyl, or indolyl,wherein each one of the above groups R₅ is substituted independently byfrom one to three of fluoro, chloro, C₁-C₆ alkyl, or C₁-C₆ alkoxy, orone of hydroxy, iodo, bromo, formyl, cyano, nitro, trifluoromethyl,amino, NH(C₁-C₄ alkyl), N(C₁-C₆)(C₁-C₂ alkyl), COOH, COO(C₁-C₄ alkyl),CO(C₁-C₄ alkyl), SO₂NH(C₁-C₄ alkyl), SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl),SO₂NH₂, NHSO₂(C₁-C₄ alkyl), S(C₁-C₆ alkyl), or SO₂(C₁-C₆ alkyl), whereinsaid C₁-C₄ alkyl and C₁-C₆ alkyl may be substituted by one or two offluoro, hydroxy, amino, methylamino, dimethylamino or acetyl; R₆ ishydrogen, or C₁-C₆ alkyl, wherein said C₁-C₆ alkyl may be substituted byone hydroxy, methoxy, ethoxy or fluoro; R₇ is hydrogen, C₁-C₄ alkyl,fluoro, chloro, bromo, iodo, cyano, hydroxy, O(C₁-C₄ alkyl), C(O)(C₁-C₄alkyl), or C(O)O(C₁-C₄ alkyl), wherein the C₁-C₄ alkyl groups may besubstituted with one hydroxy, chloro or bromo, or one to three fluoro;R₁₁ is hydrogen, hydroxy, fluoro, or methoxy; R₁₂ is hydrogen or C₁-C₄alkyl; and R₁₆ and R₁₇ are each independently hydrogen, hydroxy, methyl,ethyl, methoxy, or ethoxy, except that they are not both methoxy orethoxy, and CR₄R₆ and CR₁₆R₁₇ each independently may be C═O.
 6. Themethod of claim 2 wherein the corticotropin releasing factor antagonistis a compound of formula

and the pharmaceutically acceptable acid addition salts thereof, whereinA is N or —CR₆; B is —NR₁R₂, —CR₁R₂R₁₁,—C(═CR₂R₁₂)R₁, —NHCHR₁R₂,—OCHR₁R₂, —SCHR₁R₂, —CHR₂OR₁₂, —CHR₂SR₁₂, —C(S)R₁or —C(O)R₁; R₁ is C₁-C₆alkyl which may optionally be substituted with one or two substituentsindependently selected from the group consisting of hydroxy, fluoro,chloro, bromo, iodo, C₁-C₄ alkoxy,  O—CO—(C₁-C₄ alkyl), —O—CO—NH(C₁-C₄alkyl), —O—CO—N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —NH(C₁-C₄ alkyl), —N(C₁-C₂alkyl)(C₁-C₄ alkyl), —S(C₁-C₄ alkyl), —N(C₁-C₄alkyl)CO(C₁-C₄ alkyl),—NHCO(C₁-C₄ alkyl), —COO(C₁-C₄ alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄alkyl)(C₁-C₂ alkyl), CN, NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), andwherein any of the foregoing C₁-C₄ alkyl and C₁-C₆ alkyl groups mayoptionally contain one carbon-carbon double or triple bond; R₂ is C₁-C₁₂alkyl, aryl, —(C₁-C₄ alkylene)aryl wherein said aryl is phenyl,naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl,pyrimidyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, benzisothiazolyl, thiazolyl, isoxazolyl, benzisoxazolyl,benzimidazolyl, triazolyl, pyrazolyl, pyrrolyl, indolyl, oxazolyl, orbenzoxazolyl; or 3- to 8- membered cycloalkyl or —(C₁-C₆alkylene)cycloalkyl, wherein one or two of the ring carbons of saidcycloalkyl having at least 4 ring members and the cycloalkyl moiety ofsaid —(C₁-C₆ alkylene)cycloalkyl having at least 4 ring members mayoptionally be replaced by an oxygen or sulfur atom or by N—Z wherein Zis hydrogen; or C₁-C₄ alkyl, and wherein each of said groups R₂ mayoptionally be substituted with from one to three substituentsindependently selected from chloro, fluoro, and C₁-C₄ alkyl, or by onesubstituent selected from bromo, iodo, C₁-C₆ alkoxy, —O—CO—(C₁-C₆alkyl), —S(C₁-C₆ alkyl), —COO(C₁-C₄ alkyl), CN, NO₂, —SO(C₁-C₄ alkyl),and —SO₂(C₁-C₄ alkyl), and wherein said C₁-C₁₂ alkyl and the C₁-C₄alkylene moiety of said —(C₁-C₄ alkylene)aryl may optionally contain onecarbon-carbon double or triple bond; or —NR₁R₂ may form a saturated 5-to 8-membered heterocyclic ring, or —CHR₁R₂ may form a saturated 5- to8-membered carbocyclic ring, wherein each of these rings may optionallycontain one or two carbon-carbon double bonds and wherein one or two ofthe carbon atoms of each of these rings may optionally be replaced witha sulfur or oxygen atom; R₃ is C₁-C₄ alkyl, fluoro, chloro, bromo, iodo,—CH₂OH, —CH₂OCH₃, —O(C₁-C₃ alkyl), —S(C₁-C₃ alkyl), or —SO₂(C₁-C₃alkyl), wherein said C₁-C₃ alkyl may optionally contain onecarbon-carbon double or triple bond; R₄ is hydrogen, C₁-C₆ alkyl,fluoro, chloro, bromo, iodo, C₁-C₄ alkoxy, amino, —NHCH₃, —N(CH₃)₂,—CH₂OH, —CH₂OCH₃, or —SO_(n)(C₁-C₄ alkyl), wherein n is 0, 1 or 2,cyano, hydroxy, —CO(C₁-C₄ alkyl), —CHO, or —COO(C₁-C₄ alkyl) wherein theC₁-C₄ alkyl moieties in the foregoing R₄ groups may optionally containone carbon-carbon double or triple bond; R₅ is phenyl, naphthyl,thienyl, benzothienyl, pyridyl, pyrimidyl, benzofuranyl, pyrazinyl orbenzothiazolyl, wherein each one of said groups R₅ may optionally besubstituted with from one to three substituents independently selectedfrom fluoro, chloro, C₁-C₆ alkyl and C₁-C₆ alkoxy, or by one substituentselected from iodo, hydroxy, bromo, formyl, cyano, nitro, amino,trifluoromethyl, —NH(C₁-C₄ alkyl), —N(C₁-C₆)(C₁-C₂ alkyl), —COO(C₁-C₄alkyl), —CO(C₁-C₄ alkyl), —COOH, —SO₂NH(C₁-C₄ alkyl), —SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl), —SO₂NH₂, —NHSO₂(C₁-C₄ alkyl), —S(C₁-C₆ alkyl) and—SO₂(C₁-C₆ alkyl), wherein each of said C₁-C₄ alkyl and C₁-C₆ alkylmoieties in the foregoing R⁵ groups may optionally be substituted withone to three fluorine atoms; R₆ is hydrogen, C₁-C₄ alkyl, fluoro,chloro, bromo, iodo, —CH₂OH, —CH₂OCH₃, or C₁-C₄ alkoxy; R₇ is hydrogen,C₁-C₄ alkyl, fluoro, chloro, bromo, iodo, —O(C₁-C₄ alkyl), cyano,—CH₂OH, —CH₂O(C₁-C₂ alkyl), —CO(C₁-C₂ alkyl), or —COO(C₁-C₂ alkyl); R₁₁is hydrogen, hydroxy, fluoro, or methoxy; and R₁₂ is hydrogen or C₁-C₄alkyl; with the proviso that when A is N, then: (a) B is notunsubstituted alkyl; (b) R₅ is not unsubstituted phenyl ormonosubstituted phenyl; and (c) R₃ is not unsubstituted alkyl; or apharmaceutically acceptable salt of such compound.
 7. The method ofclaim 2 wherein the corticotropin releasing factor antagonist is acompound of formula

or a pharmaceutically acceptable salt thereof, wherein the dashed linesrepresent optional double bonds; A is nitrogen or CR⁷; B is —NR¹R²,—CR¹R²R¹⁰, —C(═CR²R¹¹)R¹, —NHCR¹R²R¹⁰, —OCR¹R²R¹⁰, —SCR¹R²R¹⁰,—CR²R¹⁰NHR¹, —CR²R¹⁰OR¹, —CR²R¹⁰SR¹ or —COR²; D is nitrogen and issingle bonded to all atoms to which it is attached, or D is carbon andis either double bonded to E in formulas I and II or double bonded tothe adjacent carbon atom common to both fused rings in formula III, or Dis CH and is single bonded to E in formulas I and II ; E is nitrogen, CHor carbon; F is oxygen, sulfur, CHR⁴ or NR⁴ when it is single bonded toE and F is nitrogen or CR⁴ when it is double bonded to E; G, when singlebonded to E, is hydrogen, C₁-C₄ alkyl, —S(C₁-C₄ alkyl), —O(C₁-C₄ alkyl),NH₂, —NH(C₁-C₄ alkyl) or —N(C₁-C₂ alkyl)(C₁-C₄ alkyl), wherein each ofthe C₁-C₄ alkyl groups of G may optionally be substituted with onehydroxy, —O(C₁-C₂ alkyl) or fluoro group; G, when double bonded to E, isoxygen, sulfur or NH; and G, when E is nitrogen and double bonded to Dor F, is absent; R¹ is hydrogen, C₁-C₆ alkyl optionally substituted withone or two substituents R⁸ independently selected from hydroxy, fluoro,chloro, bromo, iodo, C₁-C₄ alkoxy, CF₃, —C(═O)0—(C₁-C₄)alkyl,—OC(═O)(C₁-C₄ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —NHCO(C₁-C₄alkyl), —COOH, —COO(C₁-C₄ alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄alkyl)(C₁-C₂ alkyl), —S(C₁-C₄ alkyl), —CN, —NO₂, —SO(C₁-C₄ alkyl),—SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄ alkyl)(C₁-C₂alkyl), wherein each of the C₁-C₄ alkyl groups in the foregoing R′groups may optionally contain one or two double or triple bonds; R² isC₁-C₁₂ alkyl which may optionally contain from one to three double ortriple bonds, aryl or (C₁-C₄ alkylene)aryl, wherein said aryl and thearyl moiety of said (C₁-C₄ alkylene)aryl is selected from phenyl,naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl,pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridyl, oxazolyl andbenzoxazolyl; C₃-C₈ cycloalkyl or (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl),wherein one or two of the carbon atoms of said cycloalkyl and the 5 to 8membered cycloalkyl moieties of said (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl)may optionally and independently be replaced by an oxygen or sulfur atomor by NZ² wherein Z² is selected from hydrogen, C₁-C₄ alkyl, benzyl andC₁-C₄ alkanoyl, and wherein each of the foregoing R² groups mayoptionally be substituted with from one to three substituentsindependently selected from chloro, fluoro, hydroxy and C₁-C₄ alkyl, orwith one substituent selected from bromo, iodo, C₁-C₆ alkoxy,—OC(═O)(C₁-C₆ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₆alkyl), amino, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —N(C₁-C₄alkyl)—CO—(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄ alkyl),—CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —SH, —CN, —NO₂,—SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl); —NR¹R² or CR¹R²R¹⁰ may form a saturated 3 to 8membered carbocyclic ring which may optionally contain from one to threedouble bonds and wherein one or two of the ring carbon atoms of such 5to 8 membered rings may optionally and independently be replaced by anoxygen or sulfur atom or by NZ³ wherein Z³ is hydrogen, C₁-C₄ alkyl,benzyl or C₁-C₄ alkanoyl; R³ is hydrogen, C₁-C₄ alkyl, —O(C₁-C₄ alkyl),chloro, fluoro, bromo, iodo, —CN, —S(C₁-C₄ alkyl) or —SO₂(C₁-C₄ alkyl)wherein each of the (C₁-C₄ alkyl) moieties in the foregoing R³ groupsmay optionally be substituted with one substituent R⁹ selected fromhydroxy, fluoro and (C₁-C₂ alkoxy); each R⁴ is, independently, hydrogen,(C₁-C₆ alkyl), fluoro, chloro, bromo, iodo, hydroxy, cyano, amino,nitro, —O(C₁-C₄ alkyl), —N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₄ alkyl),—SO(C₁-C₄ alkyl), —SO₂(C₁-C₄)alkyl, —CO(C₁-C₄ alkyl), —C(═O)H or—C(═O)O(C₁-C₄alkyl), wherein each of the (C₁-C₆ alkyl) and (C₁-C₄ alkyl)moieties in the foregoing R⁴ groups may optionally contain one or twodouble or triple bonds and may optionally be substituted with one or twosubstituents independently selected from hydroxy, amino, C₁-C₃ alkoxy,dimethylamino, methylamino, ethylamino, —NHC(═O)CH₃, fluoro, chloro,C₁-C₃ thioalkyl, —CN, —COOH, —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄ alkyl)and —NO₂; R⁵ is phenyl, naphthyl, thienyl, benzothienyl, pyridyl,quinolyl, pyrazinyl, furanyl, benzofuranyl, benzothiazolyl,benzisothiazolyl, benzisoxazolyl, benzimidazolyl, indolyl, benzoxazolylor C₃-C₈ cycloalkyl wherein one or two of the carbon atoms of saidcycloalkyl rings that contain at least 5 ring members may optionally andindependently be replaced by an oxygen or sulfur atom or by NZ⁴ whereinZ⁴ is hydrogen, C₁-C₄ alkyl or benzyl; and wherein each of the foregoingR⁵ groups is substituted with from one to four substituents R¹² whereinone to three of said substituents may be selected, independently, fromchloro, C₁-C₆ alkyl and —O(C₁-C₆ alkyl) and one of said substituents maybe selected from bromo, iodo, formyl, —CN, —CF₃, —NO₂, —NH₂, —NH(C₁-C₄alkyl), —N(C₁-C₂ alkyl)(C₁-C₆ alkyl), —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄alkyl), —COOH, —SO₂NH(C₁-C₄ alkyl), —SO₂N(C₁-C₂ alkyl)(C₁-C₄ alkyl),—SO₂NH₂, —NHSO₂(C₁-C₄ alkyl), —S(C₁-C₆ alkyl) and —SO₂(C₁-C₆ alkyl), andwherein each of the C₁-C₄ alkyl and C₁-C₆ alkyl moieties in theforegoing R⁵ groups may optionally be substituted with one or twosubstituents independently selected from fluoro, hydroxy, amino,methylamino, dimethylamino and acetyl; R⁷ is hydrogen, C₁-C₄ alkyl,halo, cyano, hydroxy, —O(C₁-C₄ alkyl) —C(═O)(C₁-C₄ alkyl),—C(═O)O(C₁-C₄alkyl), —OCF₃, —CF₃, —CH₂OH, —CH₂O(C₁-C₄ alkyl); R¹⁰ ishydrogen, hydroxy, methoxy or fluoro; R¹¹ is hydrogen or C₁-C₄ alkyl;and Z is NH, oxygen, sulfur, —N(C₁-C₄ alkyl), —NC(═O)(C₁-C₂ alkyl),NC(═O)O(C₁-C₂alkyl) or CR¹³R¹⁴ wherein R¹³ and R¹⁴ are independentlyselected from hydrogen, trifluoromethyl and methyl with the exceptionthat one of R¹³ and R¹⁴can be cyano; with the proviso that: (a) in thefive membered rings of structures I, II and III, there can not be twodouble bonds adjacent to each other; and (b) when R⁴ is attached tonitrogen, it is not halo, cyano or nitro; or a pharmaceuticallyacceptable salt of such compound.
 8. The method of claim 2 wherein thecorticotropin releasing factor antagonist is a compound of formula

wherein the dashed lines represent optional double bonds; A is nitrogenor CR^(7;) B is —NR¹R², —CR¹R²R¹⁰, —C(═CR²R¹¹)R¹, —NHCR¹R²R¹⁰,—OCR¹R²R¹⁰—SCR¹R²R¹⁰, —CR²R¹⁰NHR¹, —CR²R¹⁰OR¹, —CR²R¹⁰SR¹or —COR², andis single bonded to D; or B is —CR¹R², and is double bonded to D and Dis carbon; D is nitrogen or CR⁴ and is single bonded to all atoms towhich it is attached, or D is carbon and is double bonded to E or doublebonded to B; E is oxygen, nitrogen, sulfur, C═O, C═S, CR⁶R¹², NR⁶ orCR⁶; or E is a two atom spacer, wherein one of the atoms is oxygen,nitrogen, sulfur, C═O, C═S, CR⁶R¹², NR6 or CR⁶, and the other is CR⁶R¹²or CR^(9;) K and G are each, independently, C═O, C═S, sulfur, oxygen,CHR⁸ or NR⁸ when single bonded to both adjacent ring atoms, or nitrogenor CR⁸ when it is double bonded to an adjacent ring atom; the 6- or7-membered ring that contains D, E, K and G may contain from one tothree double bonds, from zero to two heteroatoms selected from oxygen,nitrogen and sulfur, and from zero to two C═O or C═S groups, wherein thecarbon atoms of such groups are part of the ring and the oxygen andsulfur atoms are substituents on the ring; R¹ is C₁-C₆ alkyl optionallysubstituted with from one or two substituents independently selectedfrom hydroxy, fluoro, chloro, bromo, iodo, C₁-C₄ alkoxy, CF₃,—C(═O)(C₁-C₄alkyl), —C(═O)—O—(C₁-C₄)alkyl, —OC(═O)(C₁-C₄ alkyl),—OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —NHCO(C₁-C₄ alkyl), —COOH,—COO(C₁-C₄ alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl),—S(C₁-C₄ alkyl), —CN, —NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl),—SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), wherein each ofthe C₁-C₄ alkyl groups in the foregoing R¹ groups may optionally containone or two double or triple bonds; R² is C₁-C₁₂ alkyl which mayoptionally contain from one to three double or triple bonds, aryl or(C₁-C₄ alkylene)aryl, wherein said aryl and the aryl moiety of said(C₁-C₄ alkylene)aryl is selected from phenyl, naphthyl, thienyl,benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidinyl, imidazolyl,furanyl, benzofuranyl, benzothiazolyl, isothiazolyl, pyrazolyl,pyrrolyl, indolyl, pyrrolopyridyl, oxazolyl and benzoxazolyl; C₃-C₈cycloalkyl or (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl), wherein one or two ofthe carbon atoms of said cycloalkyl and the 5 to 8 membered cycloalkylmoieties of said (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl may optionally andindependently be replaced by an oxygen or sulfur and wherein each of theforegoing R² groups may optionally be substituted with from one to threesubstituents independently selected from chloro, fluoro, hydroxy andC₁-C₄ alkyl, or with one substituent selected from C₁-C₆ alkoxy,—OC(═O)(C₁-C₆ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₆alkyl), amino, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —N(C₁-C₄alkyl)—CO—(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄ alkyl),—CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —SH, —CN, —NO₂,—SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl); —NR¹R² or CR¹R²R¹⁰ may form a ring selected fromsaturated 3 to 8 membered rings, the 5 to 8 membered rings of which mayoptionally contain one or two double bonds, and wherein one or two ofthe ring carbon atoms of such 5 to 8 membered rings may optionally andindependently be replaced by an oxygen or sulfur atom or by NZ³ whereinZ³ is hydrogen or C₁-C₄ alkyl; R³is hydrogen, C₁-C₄ alkyl, —O(C₁-C₄alkyl), chloro, fluoro, bromo, iodo, —S(C₁-C₄ alkyl) or —SO₂(C₁-C₄alkyl); R⁴ is hydrogen, C₁-C₂ alkyl, hydroxy or fluoro; each R⁶, R⁸ andR⁹ that is attached to a carbon atom is selected, independently, fromhydrogen, C₁-C₂ alkyl, fluoro, chloro, bromo, iodo, hydroxy,hydroxymethyl, formyl, trifluoromethyl, cyano, amino, nitro, —O(C₁-C₂alkyl), —N(C₁-C₂ alkyl)(C₁-C₂ alkyl), —S(C₁-C₂ alkyl), —CO(C₁-C₂ alkyl),—C(═O)H or —C(═O)O(C₁-C₂ alkyl), wherein each of the C₁-C₂ alkylmoieties in the foregoing R⁶, R⁸, and R⁹ groups may optionally containone double or triple bond; and each R⁶, R⁸, and R⁹ that is attached to anitrogen atom is selected, independently, from hydrogen and C₁-C₄ alkyl;R⁵is substituted phenyl, naphthyl, pyridyl or pyrimidyl, wherein each ofthe foregoing R⁵ groups is substituted with from two to foursubstituents R¹⁵, wherein from one to three of said substituents may beselected, independently, from chloro, C₁-C₆ alkyl, —O(C₁-C₆ alkyl) and—(C₁-C₆alkylene)O(C₁-C₆alkyl), and wherein one of said substituents maybe selected, independently, from bromo, iodo, formyl, cyano,trifluoromethyl, nitro, amino, —NH(C₁-C₄ alkyl), —N(C₁-C₂ alkyl)(C₁-C₆alkyl), —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄ alkyl), —COOH, —SO₂NH(C₁-C₄alkyl), —SO₂N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —SO₂NH₂, —NHSO₂(C₁-C₄ alkyl),—S(C₁-C₆ alkyl) and —SO₂(C₁-C₆ alkyl), and wherein each of the C₁-C₄alkyl and C₁-C₆ alkyl moieties in the foregoing R⁵ groups may optionallybe substituted with one or two substituents independently selected fromfluoro, hydroxy, amino, methylamino, dimethylamino and acetyl; R⁷ishydrogen, methyl, halo, hydroxy, methoxy, —C(═O)(C₁-C₂ alkyl),—C(═O)O(C₁-C₂ alkyl), trifluoromethoxy, hydroxymethyl, trifluoromethylor formyl; R⁷ is hydrogen, hydroxy, methoxy or fluoro; R¹¹ is hydrogenor C₁-C₄ alkyl; R¹² is hydrogen or methyl; and Z is NH, oxygen, sulfur,—N(C₁-C₄ alkyl), or CR¹³R¹⁴ wherein R¹³ and R¹⁴ are independentlyselected from hydrogen, and methyl with the exception that one of R¹³and R¹⁴ may optionally be cyano; with the proviso that: (a) in the sixor seven membered rings of structures in formula I, there can not be twodouble bonds adjacent to each other; and (b) when D is carbon and isdouble bonded to B, then B is CR¹R^(2;) or a pharmaceutically acceptablesalt of such compound.
 9. The method of claim 2 wherein thecorticotropin releasing factor antagonist is a compound of formula

or a pharmaceutically acceptable salt thereof, wherein the dashed linesrepresent optional double bonds; A is nitrogen or CR⁷; B is—NR¹R²—CR¹R²R¹⁰ C(═CR²R¹¹)R¹, —NHCR¹R²R¹⁰, —OCR¹R²R¹⁰, —SCR¹R²R¹⁰,—CR²R¹⁰NHR¹, —CR²R¹⁰OR¹, —CR²R¹⁰SR¹or —COR²; J and K are eachindependently nitrogen or carbon and both J and K are not nitrogens; Dand E are each selected, independently, from nitrogen, CR⁴, C═O, C═S,sulfur, oxygen, CR⁴R⁶ and NR⁸; G is nitrogen or carbon; the ringcontaining D, E, G, K, and J in formula I may be a saturated orunsaturated 5-membered ring and may optionally contain one or two doublebonds and may optionally contain from one to three heteroatoms in thering and may optionally have one or two C═O or C═S groups; R¹is C₁-C₆alkyl optionally substituted with one or two substituents independentlyselected from hydroxy, fluoro, chloro, bromo, iodo, —O—(C₁-C₄ alkyl),CF₃, —C(═O)O—(C₁-C₄alkyl), —OC(═O)(C₁-C₄ alkyl), —OC(═O)N(C₁-C₄alkyl)(C₁-C₂ alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄ alkyl),—CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₄ alkyl),—CN, —NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and—SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl), wherein each of the C₁-C₄ alkyl groupsin the foregoing R¹ groups may optionally contain one or two double ortriple bonds; R² is C₁-C₁₂ alkyl which may optionally contain from oneto three double or triple bonds, aryl or (C₁-C₄ alkylene)aryl, whereinsaid aryl and the aryl moiety of said (C₁-C₄ alkylene)aryl is selectedfrom phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl,pyrazinyl, pyrimidinyl, imidazolyl, furanyl, benzofuranyl,benzothiazolyl, isothiazolyl, pyrazolyl, pyrrolyl, indolyl,pyrrolopyridyl, oxazolyl and benzoxazolyl; C₃-C₈ cycloalkyl or (C₁-C₆alkylene)(C₃-C₈ cycloalkyl), wherein one or two of the carbon atoms ofsaid cycloalkyl and the 5 to 8 membered cycloalkyl moieties of said(C₁-C₆ alkylene)(C₃-C₈ cycloalkyl) may optionally and independently bereplaced by an oxygen or sulfur atom or by NZ² wherein Z² is selectedfrom hydrogen, C₁-C₄ alkyl, benzyl and C₁-C₄ alkanoyl, and wherein eachof the foregoing R² groups may optionally be substituted with from oneto three substituents independently selected from chloro, fluoro,hydroxy and C₁-C₄ alkyl, or with one substituent selected from bromo,iodo, C₁-C₆ alkoxy, —OC(═O)(C₁-C₆ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂alkyl), —S(C₁-C₆ alkyl), amino, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄alkyl), —N(C₁-C₄ alkyl)—CO—(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COOH,—COO(C₁-C₄ alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl),—SH, —CN, —NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl)and —SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl); —NR¹R² or CR¹R²R¹⁰ may form asaturated 3 to 8 membered carbocyclic ring which may optionally containfrom one to three double bonds and wherein one or two of the ring carbonatoms of such 5 to 8 membered rings may optionally and independently bereplaced by an oxygen or sulfur atom or by NZ³ wherein Z³ is hydrogen,C₁-C₄ alkyl, benzyl or C₁-C₄ alkanoyl; R³ is hydrogen, C₁-C₄ alkyl,—O(C₁-C₄ alkyl), chloro, fluoro, bromo, iodo, (C₁-C₂ alkylene)—O—(C₁-C₂alkyl), (C₁-C₂ alkylene)—OH, or —S(C₁-C₄ alkyl); each R⁴ is,independently, hydrogen, (C₁-C₆ alkyl), fluoro, chloro, bromo, iodo,hydroxy, cyano, amino, (C₁-C₂ alkylene)—OH, CF₃, CH₂SCH₃, nitro,—O(C₁-C₄ alkyl), —N(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₄ alkyl),—CO(C₁-C₄ alkyl), —C(═O)H or —C(═O)O(C₁-C₄alkyl); R⁶ is hydrogen, methylor ethyl; R⁸ is hydrogen or C₁-C₄ alkyl; R⁵ is phenyl, pyridyl,pyrazinyl, pyrimidyl, pyridazinyl and wherein each of the foregoing R⁵groups is substituted with from one to four substituents R¹³ wherein oneto three of said substituents may be selected, independently, fromfluoro, chloro, C₁-C₆ alkyl and —O(C₁-C₆ alkyl) and one of saidsubstituents may be selected from bromo, iodo, formyl, OH, (C₁-C₄alkylene)—OH, (C₁-C₄alkylene)—O—(C₁-C₂ alkyl), —CN, —CF₃, —NO₂, —NH₂,—NH(C₁-C₄ alkyl), —N(C₁-C₂ alkyl)(C₁-C₆ alkyl), —OCO(C₁-C₄ alkyl),(C₁-C₄ alkylene)—O—(C₁-C₄ alkyl), —S(C₁-C₆ alkyl), (C₁-C₄alkylene)—S—(C₁-C₄ alkyl), —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄ alkyl),—COOH, —SO₂NH(C₁-C₄ alkyl), —SO₂N(C₁-C₂ alkyl)(C₁-C₄ alkyl), —SO₂NH₂,—NHSO₂(C₁-C₄ alkyl), —S(C₁-C₆ alkyl) and —SO₂(C₁-C₆ alkyl), and whereineach of the C₁-C₄ alkyl and C₁-C₆ alkyl moieties in the foregoing R⁵groups may optionally have one or two double bonds; R⁷is hydrogen, C₁-C₄alkyl, halo (e.g., chloro, fluoro, iodo or bromo), hydroxy, —O(C₁-C₄alkyl), —C(═O)(C₁-C₄ alkyl), —C(═O)O(C₁-C₄ alkyl), —OCF₃, —CF₃, —CH₂OHor —CH₂O(C₁-C₂ alkyl); R¹⁰ is hydrogen, hydroxy, methoxy or fluoro; R¹¹is hydrogen or C₁-C₄ alkyl; and with the proviso that: a) when both Jand K are carbons and D is CR⁴ and E is nitrogen, then G can not benitrogen; (b) when both J and K are carbons and D and G are nitrogens,then E can not be CR⁴ or C═O or C═S; (c) when both J and K are carbonsand D and E are carbons, then G can not be nitrogen; (d) when G iscarbon, it must be double banded to E; and (e) in the ring containing J,K, D, E and G, there can not be two double bonds adjacent to each other;and the pharmaceutically acceptable salts of such compounds.
 10. Themethod of claim 2 wherein the corticotropin releasing factor antagonistis a compound of formula

wherein the dashed lines represent optional double bonds; A is nitrogenor CR⁷; B is —NR¹R², —CR¹R²R¹, —C(═CR²R¹¹)R¹, —NHCR¹R²R¹⁰, —OCR¹R²R¹⁰,—SCR¹R²R¹⁰, —CR²R¹⁰NHR¹, —CR²R¹⁰OR¹, —CR²R¹⁰SR¹ or —COR²; G is nitrogenor CR⁴ and is single bonded to all atoms to which it is attached, or Gis carbon and is double bonded to K; K is nitrogen or CR⁶ when doublebonded to G or E, or K is oxygen, sulfur, C═O, C═S, CR⁶R¹² or NR⁸ whensingle bonded to both adjacent ring atoms, or K is a two atom spacer,wherein one of the two ring atoms of the spacer is oxygen, nitrogen,sulfur, C═O, C═S, CR⁶R¹², NR⁶ or CR⁶, and the other is CR⁶R¹² or CR⁹; Dand E are each, independently, C═O, C═S, sulfur, oxygen, CR⁴R⁶ or NR⁸when single bonded to both adjacent ring atoms, or nitrogen or CR⁴ whenit is double bonded to an adjacent ring atom; the 6- or 7-membered ringthat contains D, E, K and G may contain from one to three double bonds,from zero to two heteroatoms selected from oxygen, nitrogen and sulfur,and from zero to two C═O or C═S groups, wherein the carbon atoms of suchgroups are part of the ring and the oxygen and sulfur atoms aresubstituents on the ring; R¹ is C₁-C₆ alkyl optionally substituted withfrom one or two substituents independently selected from hydroxy,fluoro, chloro, bromo, iodo, C₁-C₄ alkoxy, CF₃, —C(═O)(C₁-C₄alkyl),—C(═O)—O—(C₁-C₄)alkyl, —OC(═O)(C₁-C₄ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄ alkyl), —CONH(C₁-C₄alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —S(C₁-C₄ alkyl), —CN, —NO₂,—SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and —SO₂N(C₁-C₄alkyl)(C₁-C₂ alkyl), wherein each of the C₁-C₄ alkyl groups in theforegoing R¹ groups may optionally contain one or two double or triplebonds; R² is C₁-C₁₂ alkyl which may optionally contain from one to threedouble or triple bonds, aryl or (C₁-C₄ alkylene)aryl, wherein said aryland the aryl moiety of said (C₁-C₄ alkylene)aryl is selected fromphenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl,pyrimidinyl, imidazolyl, furanyl, benzofuranyl, benzothiazolyl,isothiazolyl, pyrazolyl, pyrrolyl, indolyl, pyrrolopyridyl, oxazolyl andbenzoxazolyl; C₃-C₈ cycloalkyl or (C₁-C₆ alkylene)(C₃-C₈ cycloalkyl),wherein one or two of the carbon atoms of said cycloalkyl and the 5 to 8membered cycloalkyl moieties of said (C₁-C₆ alkylene)(C₃-C₈ cycloalkylmay optionally and independently be replaced by an oxygen or sulfur atomor by NZ wherein Z is hydrogen, C₁-C₄ alkyl or benzyl, and wherein eachof the foregoing R² groups may optionally be substituted with from oneto three substituents independently selected from chloro, fluoro,hydroxy and C₁-C₄ alkyl, or with one substituent selected from C₁-C₆alkoxy, —OC(═O)(C₁-C₆ alkyl), —OC(═O)N(C₁-C₄ alkyl)(C₁-C₂ alkyl),—S(C₁-C₆ alkyl), amino, —NH(C₁-C₂ alkyl), —N(C₁-C₂ alkyl)(C₁-C₄ alkyl),—N(C₁-C₄ alkyl)—CO—(C₁-C₄ alkyl), —NHCO(C₁-C₄ alkyl), —COOH, —COO(C₁-C₄alkyl), —CONH(C₁-C₄ alkyl), —CON(C₁-C₄ alkyl)(C₁-C₂ alkyl), —SH, —CN,—NO₂, —SO(C₁-C₄ alkyl), —SO₂(C₁-C₄ alkyl), —SO₂NH(C₁-C₄ alkyl) and—SO₂N(C₁-C₄ alkyl)(C₁-C₂ alkyl); —NR¹R² or CR¹R²R¹⁰ may form a ringselected from saturated 3 to 8 membered rings, the 5 to 8 membered ringsof which may optionally contain one or two double bonds, and wherein oneor two of the ring carbon atoms of such 5 to 8 membered rings mayoptionally and independently be replaced by an oxygen or sulfur atom orby NZ² wherein Z² is hydrogen, benzyl or C₁-C₄ alkyl; R³ is hydrogen,C₁-C₄ alkyl, —O(C₁-C₄ alkyl), chloro, fluoro, bromo, iodo, —S(C₁-C₄alkyl) or —SO₂(C₁-C₄ alkyl); each R⁸, R⁹ and R¹² is selected,independently, from hydrogen and C₁-C₂ alkyl; each R⁴ and R⁶ that isattached to a carbon atom is selected, independently, from hydrogen andC₁-C₆ alkyl, fluoro, chloro, bromo, iodo, hydroxy, hydroxy (C₁-C₂alkyl), trifluoromethyl, cyano, amino, nitro, —O(C₁-C₄ alkyl), —N(C₁-C₄alkyl)(C₁-C₂ alkyl), —CH₂SCH₃, —S(C₁-C₄ alkyl), —CO (C₁-C₄ alkyl),—C(═O)H or —C(═O)O(C₁-C₄ alkyl), wherein each of the C₁-C₂ alkylmoieties in the foregoing R⁴ and R⁶ groups may optionally contain onedouble or triple bond; and R⁶, when attached to a nitrogen atom, isselected from hydrogen and C₁-C₄ alkyl; R⁵ is substituted phenyl,naphthyl, pyridyl or pyrimidyl, wherein each of the foregoing R⁵ groupsis substituted with from two to four substituents R¹³, wherein up tothree of said substituents may be selected, independently, from chloro,C₁-C₆ alkyl, —O(C₁-C₆ alkyl) and —(C₁-C₆ alkylene)O(C₁-C₆alkyl), andwherein one of said substituents may be selected, independently, frombromo, iodo, formyl, cyano, trifluoromethyl, nitro, amino, —NH(C₁-C₄alkyl), —N(C₁-C₂ alkyl)(C₁-C₆ alkyl), —C(═O)O(C₁-C₄ alkyl), —C(═O)(C₁-C₄alkyl), —COOH, —SO₂NH(C₁-C₄ alkyl), (C₁—SO₂N(C₁-C₂ alkyl)(C₁-C₄ alkyl),—SO₂NH₂, —N HSO₂(C₁-C₄ alkyl), —(C₀-C₁alkylene)—S—(C₁-C₂alkyl),—(C₀-C₁alkylene)—SO—(C₁-C₂alkyl), —(C₀-C₁alkylene)—SO₂—(C₁-C₂alkyl) and—(C₁-C₄alkylene)—OH, and wherein each of the C₁-C₄ alkyl and C₁-C₆ alkylmoieties in the foregoing R⁵ groups may optionally be substituted withone or two substituents independently selected from fluoro, hydroxy,amino, methylamino, dimethylamino and acetyl; R⁷ is hydrogen, methyl,halo (e.g., chloro, fluoro, iodo or bromo), hydroxy, methoxy,—C(═O)(C₁-C₂ alkyl), —C(═O)O(C₁-C₂ alkyl), hydroxymethyl,trifluoromethyl or formyl; R¹⁰ is hydrogen, hydroxy, methoxy or fluoro;and R¹¹ is hydrogen or C₁-C₄ alkyl; with the proviso that in the ringcontaining D, E, K and G of formula I, there can not be two double bondsadjacent to each other; and the pharmaceutically acceptable salt of suchcompound.
 11. The method of claim 2 wherein the corticotropin releasingfactor antagonist is a compound of formula

wherein each of R¹ and R² is independently a halogen atom; a C₁-C₅hydroxyalkyl radical; C₁-C₅ alkyl; C₇-C₁₀ aralkyl; C₁-C₅ alkoxy;trifluoromethyl; nitro; nitrile; a group —SR where R is hydrogen, aC₁-C₅ alkyl radical or a C₇-C₁₀ aralkyl radical; a group S—CO—R where Ris a C₁-C₅ alkyl radical or aralkyl in which the aryl portion is C₆-C₈and the alkyl portion is C₁-C₄; a group —COOR′ where R′ is hydrogen orC₁-C₅ alkyl; a group —CONR′R″ where R′ and R″ are as defined above forR′; a group —NR′R″ where R′ and R″ are as previously defined for R′; agroup —CONRaRb or NRaRb, where Ra and Rb, taken together with thenitrogen atom to which they are attached, form a 5- to 7-memberedheterocyclic ring; or a group —NHCO—NR′R″, where R′ and R″ are asdefined above for R′; R³ is hydrogen or as defined for R¹ and R² is ahydrogen atom; C₁₋₅ alkyl; halogen; a hydroxymethyl group; or a formylgroup; R⁵ is C₁-C₅ alkyl; a C₃-C₇ cycloalkyl group; a cycloalkylalkylgroup in which the cycloalkyl portion is C₃-C₇ and the alkyl portion isC₁-C₅; or C₅-C₆ alkenyl; n is 0 or 1; R⁶ is C₁₋₅ alkyl; alkoxyalkyl inwhich the alkyl portions are C₁-C₅; C₃-C₇ cycloalkyl; a cycloalkylalkylgroup in which the cycloalkyl portion is C₃-C₇ and the alkyl portion isC₁-C₅; a cycloalkyloxyalkyl radical in which the cycloalkyl is C₃-C₇ andthe alkyl is C₁-C₄; a hydroxyalkyloxyalkyl radical in which the alkylsare C₂-C₁₀; or an alkoxyalkyloxyalkyl radical in which the alkyls areC₃-C₁₂; and Z is an optionally substituted bi- or tricyclic aromatic orheteroaromatic group; and stereoisomers and/or addition salts thereof.12. The method of claim 2 wherein the corticotropin releasing factorantagonist is a compound of formula

including the stereoisomers and the pharmaceutically acceptable acidaddition salt forms thereof, wherein R¹ is NR⁴R⁵ or OR⁵; R²isC₁-C₆alkyl, C₁-C₆alkyloxy or C₁-C₆alkylthio, R³ is hydrogen, C₁-C₆alkyl,C₁-C₆alkylsulfonyl, C₁-C₆alkylsulfoxy or C₁-C₆alkylthio; R⁴ is hydrogen,C₁-C₆alkyl, mono- or di(C₃-C₆cyloalkylmethyl, C₃-C₆cyloalkyl,C₃-C₆alkenyl, hydroxyC₁-C₆alkyl, C₁-C₆akylcarbonyloxyC₁-C₆alkyl orC₁-C₆alkyloxyC₁-C₆alkyl; R⁵is C₁-C₈alkyl, mono- ordi(C₃-C₆cycloalkyl)methyl, Ar¹CH₂, C₃-C₆alkenyl,C₁-C₆alkyloxyC₁-C₆alkyl, hydroxyC₁-C₆alkyl, thienylmethyl,furanylmethyl, C₁-C₆alkylthioC₁-C₆alkyl, morpholinyl, mono- ordi(C₁-C₆alkyl)aminoC₁₋₆alkyl, di (C₁-C₆alkyl)amino,C₁-C₆alkylcarbonylC₁-C₆alkyl, C₁-C₆alkyl substituted with imidazolyl; ora radical of formula —Alk—O—CO—Ar¹; or R⁴ and R⁵ taken together with thenitrogen atom to which they are attached may form a pyrrolidinyl,piperidinyl, homopiperidinyl or morpholinyl group, optionallysubstituted with C₁-C₆alkyl or C₁-C₆alkyloxy C₁-C₆alkyl; and Ar isphenyl; phenyl substituted with 1, 2 or 3 substituents independentlyselected from halo, C₁-C₆alkyl, trifluoromethyl, hydroxy, cyano,C₁-C₆alkyloxy, benzyloxy, C₁-C₆alkylthio, nitro, amino and mono- ordi(C₁-C₆alkyl)amino; pyridinyl; pyridinyl substituted with 1˜2 or 3substituents independently selected from halo, C₁-C₆alkyl,trifluoromethyl, hydroxy, cyano, C₁-C₆alkyloxy, benzyloxy,C₁-C₆alkylthio, nitro, amino, mono- or di(C₁-C₆alkyl)amino andpiperidinyl; and wherein said substituted phenyl may optionally befurther substituted with one or more halogens; Ar¹ is phenyl; phenylsubstituted with 1, 2 or 3 substituents each independently selected fromhalo, C₁-C₆alkyl, C₁-C₆alkyloxy, di(C₁-C₆alkyl)aminoC₁-C₆alkyl,trifluoromethyl and C₁-C₆alkyl substituted with morpholinyl; orpyridinyl; and Alk is C₁-C₆alkanediyl; with the proviso that5-methyl-3-phenyl-7-(phenylmethoxy)-pyrazolo[1,5-a]-pyrimidine and2,5-dimethyl-7-(methylamino)-3-phenyl-pyrazolo[1,5-a]pyrimidine are notincluded.
 13. The method of claim 2 wherein the corticotropin releasingfactor antagonist is a compound of formula

including the stereoisomers and the pharmaceutically acceptable acidaddition salt forms thereof, wherein X is S, SO or SO₂; R¹ is NR⁴R⁵ orOR⁵; R² is C₁-C₆alkyl, C₁-C₆alkyloxy or C₁-C₆alkylthio; R³ is hydrogen,C₁-C₆alkyl, C₁-C₆alkylsulfonyl, C₁-C₆alkylsulfoxy or C₁-C₆alkylthio; R⁴is hydrogen, C₁₋₆alkyl, mono- or di(C₃-C₆cycloalkyl)methyl,C₃-C₆cycloalkyl, C₃-C₆alkenyl, hydroxyC₁-C₆alkyl,C₁-C₆alkylcarbonyloxyC₁-C₆alkyl or C₁-C₆alkyloxyC₁-C₆alkyl; R⁵ isC₁-C₈alkyl, mono- or di(C₃-C₆cycloalkyl)methyl, Ar¹CH₂, C₃-C₆alkenyl,C₁-C₆alkyloxyC₁-C₆alkyl, hydroxyC₁-C₆alkyl, thienylmethyl,furanylmethyl, C₁-C₆alkylthioC₁-C₆alkyl, morpholinyl, mono- ordi(C₁-C₆alkyl)aminoC₁-C₆alkyl, di(C₁-C₆alkyl)amino,C₁-C₆alkylcarbonylC₁-C₆alkyl, C₁-C₆alkyl substituted with imidazolyl; ora radical of formula —Alk—O—CO—Ar 1; or R⁴ and R⁵ taken together withthe nitrogen atom to which they are attached may form a pyrrolidinyl,piperidinyl, homopiperidinyl or morpholinyl group, optionallysubstituted with C₁-C₆alkyl or C₁-C₆alkyloxyC₁-C₆alkyl; Ar is phenyl;phenyl substituted with 1, 2 or 3 substituents independently selectedfrom halo, C₁-C₆alkyl, trifluoromethyl, hydroxy, cyano, C₁-C₆alkyloxy,benzyloxy, C₁-C₆alkylthio, nitro, amino and mono- ordi(C₁-C₆alkyl)amino; pyridinyl; pyridinyl substituted with 1, 2 or 3substituents independently selected from halo, C₁-C₆alkyl,trifluoromethyl, hydroxy, cyano, C₁-C₆alkyloxy, benzyloxy,C₁-C₆alkylthio, nitro, amino, mono- or di(C₁-C₆alkyl)amino andpiperidinyl; and wherein said substituted phenyl may optionally befurther substituted with one or more halogens; Ar¹ is phenyl; phenylsubstituted with 1, 2 or 3 substituents each independently selected fromhalo, C₁-C₆alkyl, C₁-C₆alkyloxy, di(C₁-C₆alkyl)aminoC₁-C₆alkyltrifluoromethyl, and C₁-C₆alkyl substituted with morpholinyl; orpyridinyl; and Alk is C₁-C₆alkanediyl.
 14. The method of claim 2 whereinthe corticotropin releasing factor antagonist is a compound selectedfrom the group consisting of:4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine;butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-ethyl-amine;4-(butyl-ethylamino)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one;4-(1-ethylpropoxy)-2,5-dimethyl-6-(2,4,6-trimethylphenoxy)-pyrimidine;N-butyl-N-ethyl-2,5-dimethyl-NN-(2,4,6-trimethylphenyl)-pyrimidine-4,6-diamine;[4-(1-ethyl-propoxy)-3,6-dimethyl-pyridin-2-yl]-(2,4,6-trimethylphenyl)-amine;6-(ethyl-propyl-amino)-2,7-dimethyl-9-(2,4,6-trimethylphenyl)-7,9-dihydro-purin-8-one;3-{(4-methyl-benzyl)-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-propan-1-ol;diethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;2-{butyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-ethanol;dibutyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl}-amine;butyl-ethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-methyl-3-methylsultonyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-cyclopropylmethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;di-1-propyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;diallyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-chloro-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-20pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-methoxy-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;propyl-ethyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;4-(1-ethyl-propyl)-6-methyl-3-methylsultanyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidine;n-butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;di-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;ethyl-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;diethyl-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;n-butyl-ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2-{N-n-butyl-N-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-ethanol;4-(1-ethyl-propyl)-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidine;n-butyl-ethyl-[2,5-dimethyl-7-(2,4-dimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidyl-4-yl]-(1-ethyl-propyl)amine;butyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-ethylamine;[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4,b]pyridin-4-yl]-(1-methoxymethylpropyl)-amine;4-(1-methoxymethylpropoxy)-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine;(1-ethylpropyl)-[3,5,6-trimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-amine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;4-(1-ethylpropoxy)-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,6-dimethyl-4-bromophenyl)-7H-pyrrolo[2,3-b]pyridine;2,5,6-trimethyl-7-(1-propylbutyl)-4-(2,4,6-trimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenylamino)-1,3-dihydro-30imidazo[4,5-c]pyridin-2-one;9-(1-ethylpropyl)-2-methyl-6-(2,4,6-trimethylphenylamino)-7,9-dihydro-purin-8-one;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1H-imidazo[4,5-c]pyridine;1-(1-ethylpropyl)-3,6-dimethyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethylpropyl)-3,6-dimethyl-4-(2,4,6-trimethylphenylamino)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid methyl ester;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid isopropyl ester;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-3,4-dihydro-1H-[1,6]naphthyridin-2-one;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-[1,6]naphthyridine;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;1-(1-ethyl-propyl)-3,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-3,4-dihydro-1H-3-oxa-[1,6]-naphthyridin-2-one;1-(1-ethyl-propyl)-3,3,6-trimethyl-4-(2,4,6-trimethyl-phenoxy)-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine;7-(1-ethyl-propoxy)-5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;[2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine;7-(1-ethyl-propoxy)-2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;[2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-ethyl-propyl-amine;[6-bromo-5-bromomethyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-(1-ethyl-propyl)-amine;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-amine;[6-bromo-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-(1-ethyl-propyl)-methyl-amine;7-(1-ethyl-propoxy)-5-methyl-3-(2,4,6-trimethyi-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridine;4-(1-ethyl-propoxy)-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;(±)-2,5-dimethyl-4-(tetrahydro-furan-3-yloxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo-[3,2-d]pyrimidine;2,5-dimethyl-4-(S)-(tetrahydro-furan-3-yloxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo-[3,2-d]pyrimidine;2,5-dimethyl-4-(1-propyl-butoxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-sec-butylsulfanyl-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-quinolin-4-yl]-amine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(butyl-ethyl-amino)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;(butyl-ethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(propyl-ethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(diethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;4-(butyl-ethyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;(butyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(propyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidin-4-yl]-amine;(diethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-bromo-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-bromo-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-bromo-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-bromo-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,6-dimethyl-4-bromo-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-quinolin-4-yl]-amine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,6-dimethyl-4-chloro-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-chloro-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-chloro-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-chloro-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-chloro-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-chloro-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,6-dimethyl-4-chloro-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-chloro-phenyl)-quinolin-4-yl]-amine;8-(1-hydroxymethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-diethylamino-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido-[2,3-b]pyrazin-2-one;8-(ethyl-propyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-hydroxymethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(1-ethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-diethylamino-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(ethyl-propyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-hydroxymethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(1-hydroxymethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(1-ethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-diethylamino-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(ethyl-propyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(butyl-ethyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-hydroxymethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-hydroxymethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-diethylamino-5-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(ethyl-propyl-amino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;4-(2,4-dichlorophenyl)-5-methyl-2-[N-(1-(methoxymethyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;oxalate of4-(2,4-dichlorophenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methylisoquinol-5-yl)-N-propylamino]thiazole;4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-methoxycarbonylmethylindol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-chloroisoquinol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-1-methoxynaphth-2-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-trifluoromethylphenyl)-5-methyl-2-[N-6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-)chloro-4-methoxyphenyl)-5-methyl-2-[N-(2-ethoxynaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2[N-(2,3-dimethylnaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-bromo-2-methoxynaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(2,6-dimethylnaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-(methoxymethyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-(cyclopropyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;3-(2,4-dichlorophenyl)-5-methyl-7(N-propyl-N-cyclopropanemethylamino)-pyrazolo[2,3-a]pyrimidine;3-(2,4-dichlorophenyl)-5-methyl-7-(N-allyl-N-cyclopropanemethylamino)-pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N,N-diallylamino)-pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N-butyl-N-cyclopropane-methyl-amino)pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N-propyl-N-cyclopropane-methyl-amino)pyrazolo[2,3-a]pyrimidine;2-methyl-3-(4-chlorophenyl)-5-methyl-7-(N,N-dipropylamino)-pyrazolo[2,3-a]pyrimidine;3-[6-(dimethylamino)-3-pyridinyl]-2,5-dimethyl-N,N-dipropylpyrazolo[2,3-a]pyrimidin-7-amine;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidine-7-amine;3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo[2,3-a]pyrimidine;7-(N-diethylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine;7-(N-(3-cyanopropyl)-N-propylamino-2,5-dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]-pyrazolopyrimidine;[3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl]-(1-ethyl-propyl)-amine;[2-(4-chloro-2,6-dimethyl-phenoxy)-3,6-dimethyl-pyridin-4-yl]-(1-ethyl-propyl)-amine;cyclopropylmethyl-[3-(2,4-dimethyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;cyclopropylmethyl-[3-(2-methyl-4-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;cyclopropylmethyl-[3-(2,4-di-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;[3-(2-methyl-4-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-di-propyl-amine;[2,5-dimethyl-3-(2,4-dimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;[2,5-dimethyl-3-(2,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-nicotinicacid methyl ester;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N-propyl-N-cyclopropyimethyl-pyrazolo[2,3-a]pyrimidin-7-amine;and3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N-ethyl-N-cyclopropylmethyl-pyrazolo[2,3-a]pyrimidin-7-amine;15. The method of claim 14 wherein the corticotropin releasing factorantagonist is a compound selected from the group consisting of:4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine;4-(1-ethylpropoxy)-2,5-dimethyl-6-(2,4,6-trimethylphenoxy)-pyrimidine;[4-(1-ethyl-propoxy)-3,6-dimethyl-pyridin-2-yl]-(2,4,6-trimethylphenyl)-amine;3-{(4-methyl-benzyl)-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-propan-1-ol;propyl-ethyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;ethyl-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2{N-n-butyl-N-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-ethanol;[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4,b]pyridin-4-yl]-(1-methoxymethylpropyl)-amine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;2,5,6-trimethyl-7-(1-propylbutyl)-4-(2,4,6-trimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid isopropyl ester;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine;7-(1-ethyl-propoxy)-2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;4-(1-ethyl-propoxy)-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-quinolin-4-yl]-amine;(propyl-ethyl )-[2-methyl-8-(2,4,6-trimethyl-phenyl )-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;4-(1-hydroxymethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-hydroxymethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;[3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl]-(1-ethyl-propyl)-amine;cyclopropylmethyl-[3-(2,4-dimethyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;[2,5-dimethyl-3-(2,4-dimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;3-[6-(dimethylamino)-3-pyridinyl-2,5-dimethyl-N,N-dipropylpyrazolo[2,3-a]pyrimidin-7-amine;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidine-7-amine;3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo(2,3-a)pyrimidine;7-N-diethylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine;and7-(N-(3-cyanopropyl)-N-propylamino-2,5,dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]-pyrazolopyrimidine.16. The method of claim 1 which further comprises administering to saidanimal an amount of a glucocorticoid receptor antagonist; wherein theamount of the corticotropin releasing factor antagonist and the amountof the glucocorticoid receptor antagonist result in a therapeuticeffect.
 17. The method of claim 16 wherein the glucocorticoid receptorantagonist is a compound of formula IA

an isomer thereof, a prodrug of said compound or isomer, or apharmaceutically acceptable salt of said compound, isomer or prodrug;wherein m is 1 or 2; represents an optional bond; A is selected from thegroup consisting of

D is CR₇, CR₇R₁₆, N, NR₇ or O; E is C, CR₆ or N; F is CR₄, CR₄R₅ or O;G, H and I together with 2 carbon atoms from the A-ring or 2 carbonatoms from the B-ring form a 5-membered heterocyclic ring comprising oneor more N, O or S atoms; provided that there is at most one of O and Sper ring; J, K, L and M together with 2 carbon atoms from the B-ringforms a 6-membered heterocyclic ring comprising 1 or more N atoms; X isa) absent, b) —CH₂—, c) —CH(OH)—or d) —C(O)—; R₁ is a) —H, b) —Z—CF₃, c)—(C₁-C₆)alkyl, d) —(C₂-C₆)alkenyl, e) —(C₂-C₆)alkynyl, f) —CHO, g)—CH═N—OR₁₂, h) —Z—C(O)OR₁₂, i) —Z—C(O)—NR₁₂R₁₃, j) —Z—C(O)—NR₁₂—Z-het,k) —Z—NR₁₂R₁₃, l) —Z—NR₁₂het, m) —Z-het, n) —Z—O-het, o) —Z-aryl′, p)—Z—O-aryl′, q) —CHOH-aryl′or r) —C(O)-aryl′ wherein aryl′ insubstituents o) to r) is substituted independently with 0, 1 or 2 of thefollowing: —Z—OH, —Z—NR₁₂R₁₃, —Z—NR₁₂-het, —C(O)NR₁₂R₁₃,—C(O)O(C₁-C₆)alkyl, —C(O)OH, —C(O)-het, —N R₁₂—C(O)—(C₁-C₆)alkyl,—NR₁₂—C(O)—(C₂-C₆)alkenyl, —NR₁₂—C(O)—(C₂-C₆)alkynyl, —N R₁₂—C(O)—Z-het,—CN, —Z-het, —O—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃,—O—(C₁-C₃)alkyl-C(O)O(C₁-C₆)alkyl, —NR₁₂—Z—C(O)O(C₁-C₆)alkyl,—N(Z—C(O)O(C₁-C₆)alkyl)₂, —NR₁₂—Z—C(O)—NR ₁₂R₁₃, —Z—NR₁₂—SO₂-R₁₃,—NR₁₂—SO₂-het, —C(O)H, —Z—NR₁₂—Z—O(C₁-C₆)alkyl, —Z—NR₁₂—Z—NR₁₂R₁₃,—Z—NR₁₂-(C₃-C₆)cycloalkyl, —Z—N(Z—O(C₁-C₆)alkyl)₂, —SO₂R₁₂, —SOR₁₂,—SR₁₂, —SO₂NR₁₂R₁₃, —O—C(O)—(C₁-C₄)alkyl, —O—SO₂—(C₁-C₄)alkyl, -halo or—CF₃; Z for each occurrence is independently a) —(C₀-C₆)alkyl, b)—(C₂-C₆)alkenyl or c) —(C₂-C₆)alkynyl; R₂ is a) —H, b) -halo, c) —OH, d)—(C₁-C₆)alkyl substituted with 0 or 1—OH, e) —NR₁₂R₁₃, f)—Z—C(O)O(C₁-C₆)alkyl, g) —Z—C(O)NR₁₂R₁₃, h) —O—(C₁-C₆)alkyl, i)—Z—O—C(O)—(C₁-C₆)alkyl, j) —Z—O—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃, k)—Z—O—(C₁-C₃)alkyl-C(O)—O(C₁-C₆)alkyl, l) —O—(C₂-C₆)alkenyl, m)—O—(C₂-C₆)alkynyl, n) —O—Z-het, o) —COOH, p) —C(OH)R₁₂R₁₃ or q) —Z—CN;R₃ is a) —H, b) —(C₁-C₁₀)alkyl wherein 1 or 2 carbon atoms, other thanthe connecting carbon atom, may optionally be replaced with 1 or 2heteroatoms independently selected from S, O and N and wherein eachcarbon atom is substituted with 0, 1 or 2 R_(y), c) —(C₂-C₁₀)alkenylsubstituted with 0, 1 or 2 R_(y), d) -(C₂-C₁₀)alkynyl wherein 1 carbonatom, other than the connecting carbon atom, may optionally be replacedwith 1 oxygen atom and wherein each carbon atom is substituted with 0, 1or 2 R_(y), e) —CH═C═CH₂, f) —CN, g) —(C₃-C₆)cycloalkyl, h) —Z-aryl, i)—Z-het, j) —C(O)O(C₁-C₆)alkyl, k) —O(C₁-C₆)alkyl, l) —Z—S—R₁₂, m)—Z—S(O)—R₁₂, n), —Z—S(O)₂-R₁₂, o) —CF₃ p) —NR₁₂O—(C₁-C₆)alkyl or q)—CH₂OR_(Y); provided that one of R₂ and R₃ is absent when there is adouble bond between CR₂R₃ (the 7 position) and the F moiety (the 8position) of the C-ring; R_(y) for each occurrence is independently a)—OH, b) -halo, c) —Z—CF₃, d) —Z—CF(C₁-C₃ alkyl)₂, e) —CN, f) —NR₁₂R₁₃,g) —(C₃-C₆)cycloalkyl, h) —(C₃-C₆)cycloalkenyl, i) —(C₀-C₃)alkyl-aryl,j) -het or k) —N₃; or R₂ and R₃ are taken together to form a) ═CHR₁₁, b)═NOR₁₁, c) ═O, d) ═N—NR₁₂, e) ═N—NR₁₂—C(O)—R₁₂, f) oxiranyl or g)1,3-dioxolan-4-yl; R₄ and R₅ for each occurrence are independently a)—H, b) —CN, c) —(C₁-C₆)alkyl substituted with 0 to 3 halo, d)—(C₂-C₆)alkenyl substituted with 0 to 3 halo, e) —(C₂-C₆)alkynylsubstituted with 0 to 3 halo, f) —O—(C₁-C₆)alkyl substituted with 0 to 3halo, g) —O—(C₂-C₆)alkenyl substituted with 0 to 3 halo, h)—O—(C₂-C₆)alkynyl substituted with 0 to 3 halo, i) halo, j) —OH, k)(C₃-C₆)cycloalkyl or l) (C₃-C₆)cycloalkenyl; or R₄ and R₅ are takentogether to form ═O; R₆ is a) —H, b) —CN, c) —(C₁-C₆)alkyl substitutedwith 0 to 3 halo, d) —(C₂-C₆)alkenyl substituted with 0 to 3 halo, e)—(C₂-C₆)alkynyl substituted with 0 to 3 halo or f) —OH; R₇ and R₁₆ foreach occurrence are independently a) —H, b) -halo, c) —CN, d)—(C₁-C₆)alkyl substituted with 0 to 3 halo, e) —(C₂-C₆)alkenylsubstituted with 0 to 3 halo or f) —(C₂-C₆)alkynyl substituted with 0 to3 halo; provided that R₇ is other than —CN or -halo when D is NR₇; or R₇and R₁₆ are taken together to form ═O; R₈, R₉, R₁₄ and R₁₅ for eachoccurrence are independently a) —H, b) -halo, c) (C₁-C₆)alkylsubstituted with 0 to 3 halo, d) —(C₂-C₆)alkenyl substituted with 0 to 3halo, e) —(C₂-C₆)alkynyl substituted with 0 to 3 halo, f) —CN, g)—(C₃-C₆)cycloalkyl, h) —(C₃-C₆)cycloalkenyl, i) —OH, j) —O—(C₁-C₆)alkyl,k) —O—(C₁-C₆)alkenyl, l) —O—(C₁-C₆)alkynyl, m) —NR₁₂R₁₃, n) —C(O)OR₁₂ oro) —C(O)NR₁₂R₁₃; or R₈ and R₉ are taken together on the C-ring to form═O; provided that when m is 2, only one set of R₈ and R₉ are takentogether to form ═O; or R₁₄ and R₁₅ are taken together to form ═O;provided that when R₁₄ and R₅ are taken together to form ═O, D is otherthan CR₇ and E is other than C; R₁₀ is a) —(C₁-C₁₀)alkyl substitutedwith 0 to 3 substituents independently selected from -halo, —OH and —N₃,b) -(C₂-C₁₀)alkenyl substituted with 0 to 3 substituents independentlyselected from -halo, —OH and —N₃, c) —(C₂-C₁₀)alkynyl substituted with 0to 3 substituents independently selected from -halo, —OH and —N₃, d)-halo, e) —Z—CN, f) —OH, g) —Z-het, h) —Z—NR₁₂R₁₃, i) —Z—C(O)-het, j)—Z—C(O)—(C₁-C₆)alkyl, k) —Z—C(O)—NR₁₂R₁₃, l) —Z—C(O)—NR₁₂—Z—CN, m)—Z—C(O)—NR₁₂—Z-het, n) —Z—C(O)—NR₁₂—Z—aryl, o) —Z—C(O)—NR₁₂—Z—NR₁₂R₁₃,p) —Z—C(O)—NR₁₂—Z-O(C₁-C₆)alkyl, q) —(C₁-C₆)alkyl-C(O)OH, r)-Z-C(O)O(C₁-C₆)alkyl, s) —Z—O—(C₀-C₆)alkyl-het, t)—Z—O—(C₀-C₆)alkyl-aryl, u) —Z—O—(C₁-C₆)alkyl substituted with 0 to 2R_(x), v) —Z—O—(C₁-C₆)alkyl-CH(O), w) —Z—O—(C₁-C₆)alkyl-NR₁₂-het, x)—Z—O—Z-het-Z-het, y) —Z—O—Z-het-Z—NR₁₂R₁₃, z) —Z—O—Z-het-C(O)-het, al)—Z—O—Z—C(O)-het, b1) —Z—O—Z—C(O)-het-het, c1) —Z—O—Z—C(O)—(C₁-C₆)alkyl,d1) —Z—O—Z—C(S)—NR₁₂R₁₃, e1) —Z—O—Z—C(O)—NR₁₂R₁₃, f1)—Z—O—Z—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃, g1) —Z—O—Z—C(O)—O(C₁-C₆)alkyl, h1)—Z—O—Z—C(O)—OH, i1) —Z—O—Z—C(O)—NR₁₂—O(C₁-C₆)alkyl, j1)—Z—O—Z—C(O)—NR₁₂—OH, k1) —Z—O—Z—C(O)—NR₁₂—Z—NR₁₂R₁₃, I1)—Z—O—Z—C(O)—NR₁₂—Z-het, m1) —Z—O—Z—C(O)—NR₁₂—SO₂—(C₁-C₆)alkyl, n1)—Z—O—Z—C(═NR₁₂)(NR₁₂R₁₃),o1) —Z—O—Z—C(═NOR₁₂)(NR₁₂R₁₃), p1)—Z—NR₁₂—C(O)—O—Z—NR₁₂R₁₃, q1) —Z—S—C(O)—NR₁₂R₁₃, r1)—Z—O—SO₂—(C₁-C₆)alkyl, S1) —Z—O—SO₂-aryl, t21) —Z—O—SO₂—NR₁₂R₁₃, u1)—Z—O—SO₂—CF₃, v1) —Z—NR₁₂C(O)OR₁₃ or w1) —Z—NR₁₂C(O)R₁₃; or R₉ and R₁₀are taken together on the moiety of formula A-5 to form a) ═O or b)═NOR₁₂; R₁₁ is a) —H, b) —(C₁-C₅)alkyl, c) —(C₃-C₆)cycloalkyl or d)—(C₀-C₃)alkyl-aryl; R₁₂ and R₁₃ for each occurrence are eachindependently a) —H, b) —(C₁-C₆)alkyl wherein 1 or 2 carbon atoms, otherthan the connecting carbon atom, may optionally be replaced with 1 or 2heteroatoms independently selected from S, O and N and wherein eachcarbon atom is substituted with 0 to 6 halo, c) —(C₂-C₆)alkenylsubstituted with 0 to 6 halo or d) -(C₁-C₆)alkynyl wherein 1 carbonatom, other than the connecting carbon atom, may optionally be replacedwith 1 oxygen atom and wherein each carbon atom is substituted with 0 to6 halo; or R₁₂ and R₁₃ are taken together with N to form het; or R₆ andR₁₄ or R₁₅ are taken together to form 1,3-dioxolanyl; aryl is a) phenylsubstituted with 0 to 3 R_(x), b) naphthyl substituted with 0 to 3 R_(x)or c) biphenyl substituted with 0 to 3 R_(x); het is a 5-,6- or7-membered saturated, partially saturated or unsaturated ring containingfrom one (1) to three (3) heteroatoms independently selected from thegroup consisting of nitrogen, oxygen and sulfur; and including anybicyclic group in which any of the above heterocyclic rings is fused toa benzene ring or another heterocycle; and the nitrogen may be in theoxidized state giving the N-oxide form; and substituted with 0 to 3R_(x); R_(X) for each occurrence is independently a) -halo, b) —OH, c)—(C₁-C₆)alkyl, d) —(C₂-C₆)alkenyl, e) —(C₂-C₆)alkynyl, f)—O(C₁-C₆)alkyl, 9) —O(C₂-C₆)alkenyl, h) —O(C₂-C₆)alkynyl, i)—(C₀-C₆)alkyl-N R₁₂R₁₃, j) —C(O)—NR₁₂R₁₃, k) —Z—SO₂R₁₂, l)—Z-SOR₁₂, m)—Z—SR₁₂, n) —NR₁₂-SO₂R₁₃, o) —NR₁₂—C(O)—R₁₃, p) —NR₁₂—OR₁₃, q)—SO₂—NR₁₂R₁₃, r) —CN, s) —CF₃, t) —C(O)(C₁-C₆)alkyl, u) ═O, v)—Z—SO₂-phenyl or w) —Z—SO₂-het′, aryl′ is phenyl, naphthyl or biphenyl;het′ is a 5-,6- or 7-membered saturated, partially saturated orunsaturated ring containing from one (1) to three (3) heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur; and including any bicyclic group in which any of the aboveheterocyclic rings is fused to a benzene ring or another heterocycle;provided that: 1) X—R₁ is other than hydrogen or methyl; 2) when R₉ andR₁₀ are substituents on the A-ring, they are other than mono- ordi-methoxy; 3) when R₂ and R₃ are taken together to form ═CHR₁₁ or ═Owherein R₁₁ is —O(C₁-C₆)alkyl, then —X—R, is other than (C₁-C₄)alkyl; 4)when R₂ and R₃ taken together are C═O and R₉ is hydrogen on the A-ring;or when R₂ is hydroxy, R₃ is hydrogen and R₉ is hydrogen on the A-ring,then R₁₀ is other than —O—(C₁-C₆)alkyl or —O—CH₂-phenyl at the2-position of the A-ring; 5) when X—R₁ is (C₁-C₄)alkyl, (C₂-C₄)alkenylor (C₂-C₄)alkynyl, R₉ and R₁₀ are other than mono-hydroxy or ═O,including the diol form thereof, when taken together; and 6) when X isabsent, R₁ is other than a moiety containing a heteroatom independentlyselected from N, 0 or S directly attached to the juncture of the B-ringand the C-ring.
 18. The method of claim 17 wherein the glucocorticoidreceptor antagonist is a compound selected from the group consisting of:2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(4-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(2-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(3-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-; carbamic acid, [2-(dimethylamino)ethyl]-,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-2-phenanthrenylester, [4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-pyrazinyl-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2-(1-propynyl)-7-(4-pyridinylmethoxy)-,[2R-(2α,4aα,10aβ)]; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2-(1-propynyl)-7-(2-pyridinylmethoxy)-,[2R-(2α,4aα,10aβ)]; 2-phenanthrenecarbonitrile,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(1-propynyl)-,[4bS-(4bα,7α,8aβ]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-propyl-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-propyl-N-(2-pyridinylmethyl)-,[4bS -(4bα,7α,8aβ]-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-7-(3-pyridinylmethoxy)-2-(3,3,3-trifluoropropyl)-,[2S-(2α,4aα,10aβ)]-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-7-[(2-methyl-3-pyridinyl)methoxya-4a-(phenylmethyl)-2-(3,3,3-trifluoropropyl)-,[2S-(2α,4aα,10aβ)]-;2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(3,3,3-trifluoropropyl)-(4bS,7S,8aR);2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-7-methyl-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-,(4bS,7R,8aR)-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-7-methyl-4b-(phenylmethyl)-N-3-pyridinyl-,(4bS,7R,8aR)-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-7-[(2-methyl-3-pyridinyl)methoxy]-4a-(phenylmethyl)-2-(trifluoromethyl)-,(2R,4aS, 10aR)-; and 2-phenanthrenecarboxamide, 4b, 5, 6, 7, 8, 8a, 9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(trifluoromethyl)-,(4bS, 7R, 8aR)-.
 19. A pharmaceutical composition for treating orpreventing Syndrome X which comprises an amount of a corticotropinreleasing factor antagonist and a pharmaceutically acceptable vehicle,carrier or diluent.
 20. The composition of claim 19 which comprises atherapeutically effective amount of a corticotropin releasing factorantagonist.
 21. The composition of claim 20 wherein the corticotropinreleasing factor antagonist is a compound selected from the groupconsisting of:4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine;butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-ethyl-amine;4-(butyl-ethylamino)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one;4-(1-ethylpropoxy)-2,5-dimethyl-6-(2,4,6-trimethylphenoxy)-pyrimidine;N-butyl-N-ethyl-2,5-dimethyl-NN-(2,4,6-trimethylphenyl)-pyrimidine-4,6-diamine;[4-(1-ethyl-propoxy)-3,6-dimethyl-pyridin-2-yl]-(2,4,6-trimethylphenyl)-amine;6-(ethyl-propyl-amino)-2,7-dimethyl-9-(2,4,6-trimethylphenyl)-7,9-dihydro-purin-8-one;3-{(4-methyl-benzyl)-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-propan-1-ol;diethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;2-{butyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-ethanol;dibutyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl}-amine;butyl-ethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-methyl-3-methylsulfonyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-cyclopropylmethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;di-1-propyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;diallyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-chloro-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-methoxy-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;propyl-ethyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;4-(1-ethyl-propyl)-6-methyl-3-methylsulfanyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidine;n-butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;di-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;ethyl-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;diethyl-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;n-butyl-ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2-{N-n-butyl-N-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-ethanol;4-(1-ethyl-propyl)-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidine;n-butyl-ethyl-[2,5-dimethyl-7-(2,4-dimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidyl-4-yl]-(1-ethyl-propyl)amine;butyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-ethylamine;[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4,b]pyridin-4-yl]-(1-methoxymethylpropyl)-amine;4-(1-methoxymethylpropoxy)-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine;(1-ethylpropyl)-[3,5,6-trimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-amine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;4-(1-ethylpropoxy)-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,6-dimethyl-4-bromophenyl)-7H-pyrrolo[2,3-b]pyridine;2,5,6-trimethyl-7-(1-propylbutyl)-4-(2,4,6-trimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenylamino)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;9-(1-ethylpropyl)-2-methyl-6-(2,4,6-trimethylphenylamino)-7,9-dihydro-purin-8-one;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1H-imidazo[4,5-c]pyridine;1-(1-ethylpropyl)-3,6-dimethyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethylpropyl)-3,6-dimethyl-4-(2,4,6-trimethyphenylamino)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid methyl ester;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid isopropyl ester;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-3,4-dihydro-1H-[1,6]naphthyridin-2-one;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-[1,6]naphthyridine;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;1-(1-ethyl-propyl)-3,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-3,4-dihydro-1H-3-oxa-[1,6]-naphthyridin-2-one;1-(1-ethyl-propyl)-3,3,6-trimethyl-4-(2,4,6-trimethyl-phenoxy)-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine;7-(1-ethyl-propoxy)-5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;[2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine;7-(1-ethyl-propoxy)-2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;[2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-ethyl-propyl-amine;6-bromo-5-bromomethyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-(1-ethyl-propyl)-amine;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-amine;[6-bromo-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-(1-ethyl-propyl)-methyl-amine;7-(1-ethyl-propoxy)-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridine;4-(1-ethyl-propoxy)-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;(±)-2,5-dimethyl-4-(tetrahydro-furan-3-yloxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo-[3,2-d]pyrimidine;2,5-dimethyl-4-(S)-(tetrahydro-furan-3-yloxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo-[3,2-d]pyrimidine;2,5-dimethyl-4-(1-propyl-butoxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-sec-butylsulfanyl-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-quinolin-4-yl]-amine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(butyl-ethyl-amino)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;(butyl-ethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(propyl-ethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(diethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;4-(butyl-ethyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;(butyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(propyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidin-4-yl]-amine;(diethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-bromo-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-bromo-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-bromo-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-bromo-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,6-dimethyl-4-bromo-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-quinolin-4-yl]-amine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,6-dimethyl-4-chloro-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-chloro-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-chloro-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-chloro-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-chloro-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-chloro-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,6-dimethyl-4-chloro-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-chloro-phenyl)-quinolin-4-yl]-amine;8-(1-hydroxymethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-diethylamino-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido-[2,3-b]pyrazin-2-one;8-(ethyl-propyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-hydroxymethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(1-ethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-diethylamino-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(ethyl-propyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-hydroxymethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(1-hydroxymethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(1-ethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-diethylamino-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(ethyl-propyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(butyl-ethyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-hydroxymethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-hydroxymethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-diethylamino-5-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(ethyl-propyl-amino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene4-(2,4-dichlorophenyl)-5-methyl-2-[N-(1-(methoxymethyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole; oxalate of4-(2,4-dichlorophenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methylisoquinol-5-yl)-N-propylamino]thiazole;4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-methoxycarbonylmethylindol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-chloroisoquinol-5-yl)-N-propylamino]thiazole; oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-1-methoxynaphth-2-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-trifluoromethylphenyl)-5-methyl-2-[N-6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(2-ethoxynaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2[N-(2,3-dimethylnaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-bromo-2-methoxynaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(2,6-dimethylnaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-(methoxymethyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-(cyclopropyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;3-(2,4-dichlorophenyl)-5-methyl-7(N-propyl-N-cyclopropanemethylamino)-pyrazolo[2,3-a]pyrimidine;3-(2,4-dichlorophenyl)-5-methyl-7-(N-allyl-N-cyclopropanemethylamino)-pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N,N-diallylamino)-pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N-butyl-N-cyclopropane-methyl-amino)pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N-propyl-N-cyclopropane-methyl-amino)pyrazolo[2,3-a]pyrimidine;2-methyl-3-(4-chlorophenyl)-5-methyl-7-(N,N-dipropylamino)-pyrazolo[2,3-a]pyrimidine;3-[6-(dimethylamino)-3-pyridinyl]-2,5-dimethyl-N,N-dipropylpyrazolo[2,3-a]pyrimidin-7-amine;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidine-7-amine;3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo(2,3-a)pyrimidine;7-(N-diethylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine;7-(N-(3-cyanopropyl)-N-propylamino-2,5,dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]-pyrazolopyrimidine;[3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl]-(1-ethyl-propyl)-amine;[2-(4-chloro-2,6-dimethyl-phenoxy)-3,6-dimethyl-pyridin-4-yl]-(1-ethyl-propyl)-amine;cyclopropylmethyl-[3-(2,4-dimethyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;cyclopropylmethyl-[3-(2-methyl-4-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;cyclopropylmethyl-[3-(2,4-di-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;[3-(2-methyl-4-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-di-propyl-amine;[2,5-dimethyl-3-(2,4-dimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;[2,5-dimethyl-3-(2,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-nicotinicacid methyl ester;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N-propyl-N-cyclopropylmethyl-pyrazolo[2,3-a]pyrimidin-7-amine;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N-ethyl-N-cyclopropylmethyl-pyrazolo[2,3-a]pyrimidin-7-amine;22. The composition of claim 21 wherein the corticotropin releasingfactor antagonist is a compound selected from the group consisting of:4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine;4-(1-ethylpropoxy)-2,5-dimethyl-6-(2,4,6-trimethylphenoxy)-pyrimidine;[4-(1-ethyl-propoxy)-3,6-dimethyl-pyridin-2-yl]-(2,4,6-trimethylphenyl)-amine;3-{(4-methyl-benzyl)-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-propan-1-ol;propyl-ethyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;ethyl-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2-{N-n-butyl-N-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-ethanol;[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4,b]pyridin-4-yl]-(1-methoxymethylpropyl)-amine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;2,5,6-trimethyl-7-(1-propylbutyl)-4-(2,4,6-trimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid isopropyl ester;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine;7-(1-ethyl-propoxy)-2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;4-(1-ethyl-propoxy)-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-quinolin-4-yl]-amine;(propyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidine;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;4-(1-hydroxymethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-hydroxymethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;[3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl]-(1-ethyl-propyl)-amine;cyclopropylmethyl-[3-(2,4-dimethyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;[2,5-dimethyl-3-(2,4-dimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;3-[6-(dimethylamino)-3-pyridinyl-2,5-dimethyl-N,N-dipropylpyrazolo[2,3-a]pyrimidin-7-amine;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidine-7-amine;3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo(2,3-a)pyrimidine;7-(N-diethylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine;and7-(N-(3-cyanopropyl)-N-prbpylamino-2,5,dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]-pyrazolopyrimidine.23. The composition of claim 19 which further comprises an amount of aglucocorticoid receptor antagonist and a pharmaceutically acceptablevehicle, carrier or diluent; wherein the amount of the corticotropinreleasing factor antagonist and the amount of the glucocorticoidreceptor antagonist result in a therapeutic effect.
 24. The compositionof claim 23 wherein the glucocorticoid receptor antagonist is a compoundof formula IA

an isomer thereof, a prodrug of said compound or isomer, or apharmaceutically acceptable salt of said compound, isomer or prodrug;wherein m is 1 or 2; represents an optional bond; A is selected from thegroup consisting of

D is CR₇, CR₇R₁₆, N, NR₇ or O; E is C, CR₆ or N; F is CR₄, CR₄R₅ or O;G, H and I together with 2 carbon atoms from the A-ring or 2 carbonatoms from the B-ring form a 5-membered heterocyclic ring comprising oneor more N, O or S atoms; provided that there is at most one of O and Sper ring; J, K, L and M together with 2 carbon atoms from the B-ringforms a 6-membered heterocyclic ring comprising 1 or more N atoms; X isa) absent, b) —CH₂—, c) —CH(OH)— or d) —C(O)—; R₁ is a) —H, b) —Z—CF₃,c) —(C₁-C₆)alkyl, d) —(C₂-C₆)alkenyl, e) —(C₂-C₆)alkynyl, f) —CHO, g)—CH═N—OR₁₂, h) —Z—C(O)OR₁₂, i) —Z—C(O)—NR₁₂R₁₃, j) —Z—C(O)—NR₁₂—Z-het,k) —Z—NR₁₂R₁₃, l) —Z—NR₁₂het, m) —Z-het, n) —Z—O-het, o) —Z-aryl′, p)—Z—O-aryl′, q) —CHOH-aryl′ or r) —C(O)-aryl′ wherein aryl′ insubstituents o) to r) is substituted independently with 0, 1 or 2 of thefollowing: —Z—OH, —Z—NR₁₂R₁₃, —Z—NR₁₂-het, —C(O)NR₁₂R₁₃,—C(O)O(C₁-C₆)alkyl, —C(O)OH, —C(O)-het, —NR₁₂—C(O)—(C₁-C₆)alkyl,—NR₁₂—C(O)—(C₂-C₆)alkenyl, —NR₁₂—C(O)—(C₂-C₆)alkynyl, —NR₁₂—C(O)—Z-het,—CN, —Z-het, —O—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃,—O—(C₁-C₃)alkyl-C(O)O(C₁-C₆)alkyl, —NR₁₂-Z—C(O)O(C₁-C₆)alkyl,—N(Z—C(O)O(C₁-C₆)alkyl)₂, —NR₁₂—Z—C(O)—NR₁₂R₁₃, —Z—NR₁₂—SO₂—R₁₃,—NR₁₂—SO₂-het, —C(O)H, —Z—NR₁₂—Z—O(C₁-C₆)alkyl, —Z—NR₁₂—Z—NR₁₂R₁₃, —Z—NR₁₂-(C₃-C₆)cycloalkyl, —Z—N(Z—O(C₁-C₆)alkyl)₂, —SO₂R₁₂, —SOR₁₂, —SR₁₂,—SO₂NR₁₂R₁₃, —O—C(O)—(C₁-C₄)alkyl, —O—SO₂—(C₁-C₄)alkyl, -halo or —CF₃; Zfor each occurrence is independently a) —(C₀-C₆)alkyl, b)—(C₂-C₆)alkenyl or c) —(C₂-C₆)alkynyl; R₂ is a) —H, b) -halo, c) —OH, d)—(C₁-C₆)alkyl substituted with 0 or 1—OH, e) —NR₁₂R₁₃, f)—Z—C(O)O(C₁-C₆)alkyl, g) —Z—C(O)NR₁₂R₁₃, h) —O—(C₁-C₆)alkyl, i)—Z—O—C(O)—(C₁-C₆)alkyl, j) —Z—O—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃, k)—Z—O—(C₁-C₃)alkyl-C(O)—O(C₁-C₆)alkyl, l) —O—(C₂-C₆)alkenyl, m)—O—(C₂-C₆)alkynyl, n) —O—Z-het, o) —COOH, p) —C(OH)R₁₂R₁₃ or q) —Z—CN;R₃ is a) —H, b) —(C₁-C₁₀)alkyl wherein 1 or 2 carbon atoms, other thanthe connecting carbon atom, may optionally be replaced with 1 or 2heteroatoms independently selected from S, O and N and wherein eachcarbon atom is substituted with 0, 1 or 2 R_(y), c) —(C₂-C₁₀)alkenylsubstituted with 0, 1 or 2 R_(y), d) —(C₂-C₁₀)alkynyl wherein 1 carbonatom, other than the connecting carbon atom, may optionally be replacedwith 1 oxygen atom and wherein each carbon atom is substituted with 0, 1or 2 R_(y), e) —CH═C═CH₂, f) —CN, g) —(C₃-C₆)cycloalkyl, h) —Z-aryl, i)—Z-het, j) —C(O)O(C₁-C₆)alkyl, k) —O(C₁-C₆)alkyl, l) —Z—S—R₁₂, m)—Z—S(O)—R₁₂, n) —Z—S(O)₂—R₁₂, o) —CF₃ p) —NR₁₂O—(C₁-C₆)alkyl or q)—CH₂OR_(y); provided that one of R₂ and R₃ is absent when there is adouble bond between CR₂R₃ (the 7 position) and the F moiety (the 8position) of the C-ring; R_(y) for each occurrence is independently a)—OH, b) -halo, c) —Z—CF₃, d) —Z—CF(C₁-C₃ alkyl)₂, e) —CN, f) —NR₁₂R₁₃ 9)—(C₃-C₆)cycloalkyl, h) —(C₃-C₆)cycloalkenyl, i) —(C₀-C₃)alkyl-aryl, j)-het or k) —N₃; or R₂ and R₃ are taken together to form a) ═CHR₁₁, b)═NOR,,, c) ═O, d) ═N—NR₁₂, e) ═N—NR₁₂—C(O)—R₁₂, f) oxiranyl or g)1,3-dioxolan-4-yl; R₄ and R₅ for each occurrence are independently a)—H, b) —CN, c) —(C₁-C₆)alkyl substituted with 0 to 3 halo, d)—(C₂-C₆)alkenyl substituted with 0 to 3 halo, e) —(C₂-C₆)alkynylsubstituted with 0 to 3 halo, f) —O—(C₁-C₆)alkyl substituted with 0 to 3halo, g) —O—(C₂-C₆)alkenyl substituted with 0 to 3 halo, h)—O—(C₂-C₆)alkynyl substituted with 0 to 3 halo, i) halo, j) —OH, k)(C₃-C₆)cycloalkyl or l) (C₃-C₆)cycloalkenyl; or R₄ and R₅ are takentogether to form ═O; R₆ is a) —H, b) —CN, c) —(C₁-C₆)alkyl substitutedwith 0 to 3 halo, d) —(C₂-C₆)alkenyl substituted with 0 to 3 halo, e)—(C₂-C₆)alkynyl substituted with 0 to 3 halo or f) —OH; R₇ and R₁₆ foreach occurrence are independently a) —H, b) -halo, c) —CN, )—(C₁-C₆)alkyl substituted with 0 to 3 halo, e) —(C₂-C₆)alkenylsubstituted with 0 to 3 halo or f) —(C₂-C₆)alkynyl substituted with 0 to3 halo; provided that R₇ is other than —CN or -halo when D is NR₇; or R₇and R₁₆ are taken together to form ═O; R₈, R₉, R₁₄ and R₁₅ for eachoccurrence are independently a) —H, b) -halo, c) (C₁-C₆)alkylsubstituted with 0 to 3 halo, d) —(C₂-C₆)alkenyl substituted with 0 to 3halo, e) —(C₂-C₆)alkynyl substituted with 0 to 3 halo, f) —CN, g)—(C₃-C₆)cycloalkyl, h) —(C₃-C₆)cycloalkenyl, i) —OH, j) —O—(C₁-C₆)alkyl,k) —O—(C₁-C₆)alkenyl, l) —O—(C₁-C₆)alkynyl, m) —NR₁₂R₁₃, n) —C(O)OR₁₂ oro) —C(O)NR₁₂R₁₃; or R₈ and R₉ are taken together on the C-ring to form═O; provided that when m is 2, only one set of R₈ and R₉ are takentogether to form ═O; or R₁₄ and R₁₅ are taken together to form ═O;provided that when R₁₄ and R₁₅ are taken together to form ═O, D is otherthan CR₇ and E is other than C; R₁₀ is a) —(C₁-C₁₀)alkyl substitutedwith 0 to 3 substituents independently selected from -halo, —OH and —N₃,b) —(C₂-C₁₀)alkenyl substituted with 0 to 3 substituents independentlyselected from -halo, —OH and —N₃, c) —(C₂-C₁₀)alkynyl substituted with 0to 3 substituents independently selected from -halo, —OH and —N₃, d)-halo, e) —Z—CN, f) —OH, g) —Z-het, h) —Z—NR₁₂R₁₃, i) —Z—C(O)-het, j)—Z—C(O)—(C₁-C₆)alkyl, k) —Z—C(O)—NR₁₂R₁₃, l) —Z—C(O)—NR₁₂—Z—CN, m)—Z—C(O)—NR₁₂—Z-het, n) —Z—C(O)—NR₁₂—Z-aryl, o) —Z—C(O)—NR₁₂—Z—NR₁₂R₁₃,p) —Z—C(O)—NR₁₂—Z—O(C₁-C₆)alkyl, q) —(C₁-C₆)alkyl-C(O)OH, r)—Z—C(O)O(C₁-C₆)alkyl, s) —Z—O—(C₀-C₆)alkyl-het, t)—Z—O—(C₀-C₆)alkyl-aryl, u) —Z—O—(C₁-C₆)alkyl substituted with 0 to 2R_(x), v) —Z—O—(C₁-C₆)alkyl-CH(O), w) —Z—O—(C₁-C₆)alkyl-NR₁₂-het, x)—Z—O—Z-het-Z-het, y) —Z—O—Z-het-Z-NR₁₂R₁₃, z) —Z—O—Z-het-C(O)-het, a1)—Z—O—Z—C(O)-het, b1) —Z—O—Z—C(O)-het-het, C₁) —Z—O—Z—C(O)—(C₁-C₆)alkyl,d1) —Z—O—Z—C(S)—NR₁₂R₁₃, e1) —Z—O—Z—C(O)—NR₁₂R₁₃, f1)—Z—O—Z—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃, g1) —Z—O—Z—C(O)—O(C₁-C₆)alkyl, h1)—Z—O—Z—C(O)—OH, i1) —Z—O—Z—C(O)—NR₁₂—O(C₁-C₆)alkyl, j1)—Z—O—Z—C(O)—NR₁₂—OH, k1) —Z—O—Z—C(O)—NR₁₂—Z—NR₁₂R₁₃, l1)—Z—O—Z—C(O)—NR₁₂—Z-het, m1) —Z—O—Z—C(O)—NR₁₂—SO₂—(C₁-C₆)alkyl, n1)—Z—O—Z—C(═NR₁₂)(NR₁₂R₁₃), o1) —Z—O—Z—C(═NOR₁₂)(NR₁₂R₁₃), p1)—Z—NR₁₂—C(O)—O—Z—NR₁₂R₁₃, q1) —Z—S—C(O)—NR₁₂R₁₃, r1)—Z—O—SO₂—(C₁-C₆)alkyl, s1) —Z—O—SO₂-aryl, t1) —Z—O—SO₂—NR₁₂R₁₃, u1)—Z—O—SO₂—CF₃, v1) —Z—NR₁₂C(O)OR₁₃ or w1) —Z—NR₁₂C(O)R₁₃; or R₉ and R₁₀are taken together on the moiety of formula A-5 to form a) ═O or b)═NOR₁₂; R₁₁ is a) —H, b) —(C₁-C₅)alkyl, c) —(C₃-C₆)cycloalkyl or d)—(CO—C₃)alkyl-aryl; R₁₂ and R₁₃ for each occurrence are eachindependently a) —H, b) —(C₁-C₆)alkyl wherein 1 or 2 carbon atoms, otherthan the connecting carbon atom, may optionally be replaced with 1 or 2heteroatoms independently selected from S, O and N and wherein eachcarbon atom is substituted with 0 to 6 halo, c) —(C₂-C₆)alkenylsubstituted with 0 to 6 halo or d) —(C₁-C₆)alkynyl wherein 1 carbonatom, other than the connecting carbon atom, may optionally be replacedwith 1 oxygen atom and wherein each carbon atom is substituted with 0 to6 halo; or R₁₂ and R₁₃ are taken together with N to form het; or R₆ andR₁₄ or R₁₅ are taken together to form 1,3-dioxolanyl; aryl is a) phenylsubstituted with 0 to 3 R_(x), b) naphthyl substituted with 0 to 3 R_(x)or c) biphenyl substituted with 0 to 3 R_(x); het is a 5-,6- or7-membered saturated, partially saturated or unsaturated ring containingfrom one (1) to three (3) heteroatoms independently selected from thegroup consisting of nitrogen, oxygen and sulfur; and including anybicyclic group in which any of the above heterocyclic rings is fused toa benzene ring or another heterocycle; and the nitrogen may be in theoxidized state giving the N-oxide form; and substituted with 0 to 3 R,;R_(x) for each occurrence is independently a) -halo, b) —OH, c)—(C₁-C₆)alkyl, d) —(C₂-C₆)alkenyl, e) —(C₂-C₆)alkynyl, f)—O(C₁-C₆)alkyl, g) —O(C₂-C₆)alkenyl, h) —O(C₂-C₆)alkynyl, i)—(C₀-C₆)alkyl-NR₁₂R₁₃, j) —C(O)—NR₁₂R₁₃, k) —Z—SO₂R₁₂, l)—Z-SOR₁₂, m)—Z—SR₁₂, n) —NR₁₂—SO₂R₁₃, o) —NR₁₂—C(O)—R₁₃, p) —NR₁₂—OR₁₃, q)—SO₂—NR₁₂R₁₃, r) —CN, s) —CF₃, t) —C(O)(C₁-C₆)alkyl, u) ═O, v)—Z—SO₂-phenyl or w) —Z—SO₂-het′; aryl′ is phenyl, naphthyl or biphenyl;het′ is a 5-,6- or 7-membered saturated, partially saturated orunsaturated ring containing from one (1) to three (3) heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur; and including any bicyclic group in which any of the aboveheterocyclic rings is fused to a benzene ring or another heterocycle;provided that: 1) X—R₁ is other than hydrogen or methyl; 2) when R₉ andR₁₀ are substituents on the A-ring, they are other than mono- ordi-methoxy; 3) when R₂ and R₃ are taken together to form ═CHR₁₁ or ═Owherein R₁₁ is —O(C₁-C₆)alkyl, then —X—R₁ is other than (C₁-C₄)alkyl; 4)when R₂ and R₃ taken together are C═O and R₉ is hydrogen on the A-ring;or when R₂ is hydroxy, R₃ is hydrogen and R₉ is hydrogen on the A-ring,then R₁₀ is other than —O—(C₁-C₆)alkyl or —O—CH₂-phenyl at the2-position of the A-ring; 5) when X—R₁ is (C₁-C₄)alkyl, (C₂-C₄)alkenylor (C₂-C₄)alkynyl, R₉ and R₁₀ are other than mono-hydroxy or ═O,including the diol form thereof, when taken together; and 6) when X isabsent, R₁ is other than a moiety containing a heteroatom independentlyselected from N, O or S directly attached to the juncture of the B-ringand the C-ring.
 25. The composition of claim 24 wherein theglucocorticoid receptor antagonist is a compound selected from the groupconsisting of: 2-phenanthrenecarboxamide, 4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(4-pyridinylmethyl)-,[4bS-(4bα,7α, 8αβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(2-pyridinylmethyl)-,[4bS-(4bα,7α,8αβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(3-pyridinylmethyl)-,[4bS-(4bα,7α,8αβ)]-; carbamic acid, [2-(dimethylamino)ethyl]-,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-2-phenanthrenylester, [4bS-(4bα,7α,8αβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-pyrazinyl-,[4bS-(4bα,7α,8αβ)]-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2-(1-propynyl)-7-(4-pyridinylmethoxy)-,[2R-(2α,4aα,10aβ)]; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2-(1-propynyl)-7-(2-pyridinylmethoxy)-,[2R-(2α,4aα,10aβ)]; 2-phenanthrenecarbonitrile,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(1-propynyl)-,[4bS-(4bα,7α,8aβ)]-;2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-propyl-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-propyl-N-(2-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-7-(3-pyridinylmethoxy)-2-(3,3,3-trifluoropropyl)-,[2S-(2α,4aα, 10aβ)]-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-7-[(2-methyl-3-pyridinyl)methoxy]-4a-(phenylmethyl)-2-(3,3,3-trifluoropropyl)-,[2S-(2α,4aα,10aβ)]-;2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(3,3,3-trifluoropropyl)-,(4bS,7S,8aR); 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-7-methyl-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-,(4bS,7R,8aR)-;2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-7-methyl-4b-(phenylmethyl)-N-3-pyridinyl-,(4bS,7R,8aR)-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-7-[(2-methyl-3-pyridinyl)methoxy]-4a-(phenylmethyl)-2-(trifluoromethyl)-,(2R,4aS,10aR)-; and 2-phenanthrenecarboxamide, 4b, 5, 6, 7, 8, 8a, 9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(trifluoromethyl)-, (4bS, 7R, 8aR)-.
 26. A kit which comprises an amount of acorticotropin releasing factor antagonist and a pharmaceuticallyacceptable vehicle, carrier or diluent in a first unit dosage form; anamount of a glucocorticoid receptor antagonist and a pharmaceuticallyacceptable vehicle, carrier or diluent in a second unit dosage form; anda container for containing said first and second dosage forms; whereinthe amount of the corticotropin releasing factor antagonist and theamount of the glucocorticoid receptor antagonist result in a therapeuticeffect.
 27. The kit of claim 26 wherein the corticotrophin releasingfactor antagonist is a compound selected from the group consisting of:4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine;butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl]-ethyl-amine;4-(butyl-ethylamino)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-one;4-(1-ethylpropoxy)-2,5-dimethyl-6-(2,4,6-trimethylphenoxy)-pyrimidine;N-butyl-N-ethyl-2,5-dimethyl-NN-(2,4,6-trimethylphenyl)-pyrimidine-4,6-diamine;[4-(1-ethyl-propoxy)-3,6-dimethyl-pyridin-2-yl]-(2,4,6-trimethylphenyl)-amine;6-(ethyl-propyl-amino)-2,7-dimethyl-9-(2,4,6-trimethylphenyl)-7,9-dihydro-purin-8-one;3-{(4-methyl-benzyl)-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-propan-1-ol;diethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;2-{butyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-ethanol;dibutyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl}-amine;butyl-ethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-methyl-3-methylsulfonyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-cyclopropylmethyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;di-1-propyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;diallyl-[6-methyl-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-chloro-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;butyl-ethyl-[6-methoxy-3-methylsulfanyl-1-(2,4,6-trichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;propyl-ethyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;4-(1-ethyl-propyl)-6-methyl-3-methylsulfanyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidine;n-butyl-ethyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;di-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;ethyl-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;diethyl-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;n-butyl-ethyl-[2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2-{N-n-butyl-N-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-ethanol;4-(1-ethyl-propyl)-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidine;n-butyl-ethyl-[2,5-dimethyl-7-(2,4-dimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidyl-4-yl]-(1-ethyl-propyl)amine;butyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-ethylamine;[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4,b]pyridin-4-yl]-(1-methoxymethylpropyl)-amine;4-(1-methoxymethylpropoxy)-3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridine;(1-ethylpropyl)-[3,5,6-trimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]-amine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;4-(1-ethylpropoxy)-2,5,6-trimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,6-dimethyl-4-bromophenyl)-7H-pyrrolo[2,3-b]pyridine;2,5,6-trimethyl-7-(1-propylbutyl)-4-(2,4,6-trimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenylamino)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;9-(1-ethylpropyl)-2-methyl-6-(2,4,6-trimethylphenylamino)-7,9-dihydro-purin-8-one;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1H-imidazo[4,5-c]pyridine;1-(1-ethylpropyl)-3,6-dimethyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethylpropyl)-3,6-dimethyl-4-(2,4,6-trimethylphenylamino)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid methyl ester;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid isopropyl ester;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-3,4-dihydro-1H-[1,6]naphthyridin-2-one;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-[1,6]naphthyridine;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;1-(1-ethyl-propyl)-3,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-3,4-dihydro-1H-3-oxa-[1,6]-naphthyridin-2-one;1-(1-ethyl-propyl)-3,3,6-trimethyl-4-(2,4,6-trimethyl-phenoxy)-2,3-dihydro-1H-pyrrolo[3,2-c]pyridine;7-(1-ethyl-propoxy)-5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;[2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine;7-(1-ethyl-propoxy)-2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;[2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-ethyl-propyl-amine;[6-bromo-5-bromomethyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-(1-ethyl-propyl)-amine;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-amine;[6-bromo-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-7-yl]-(1-ethyl-propyl)-methyl-amine;7-(1-ethyl-propoxy)-5-methyl-3-(2,4,6-trimethyl-phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridine;4-(1-ethyl-propoxy)-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;(±)-2,5-dimethyl-4-(tetrahydro-furan-3-yloxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo-[3,2-d]pyrimidine;2,5-dimethyl-4-(S)-(tetrahydro-furan-3-yloxy)-7-)2,4,6-trimethyl-phenyl)-5H-pyrrolo-[3,2-d]pyrimidine;2,5-dimethyl-4-(1-propyl-butoxy)-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-sec-butylsulfanyl-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-quinolin-4-yl]-amine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(butyl-ethyl-amino)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;(butyl-ethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(propyl-ethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(diethyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;4-(butyl-ethyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;(butyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(propyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidin-4-yl]-amine;(diethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-bromo-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-bromo-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-bromo-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-bromo-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,6-dimethyl-4-bromo-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-bromo-phenyl)-quinolin-4-yl]-amine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,6-dimethyl-4-chloro-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-chloro-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,6-dimethyl-4-chloro-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,6-dimethyl-4-chloro-phenyl)-quinoline;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-chloro-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propoxy)-7-methyl-1-(2,6-dimethyl-4-chloro-phenyl)-1,2-dihydro-3-oxa-1,8-diaza-naphthalen-4-one;8-(1-ethyl-propoxy)-1,6-dimethyl-4-(2,6-dimethyl-4-chloro-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;(1-ethyl-propyl)-[2-methyl-8-(2,6-dimethyl-4-chloro-phenyl)-quinolin-4-yl]-amine;8-(1-hydroxymethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-ethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-diethylamino-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido-[2,3-b]pyrazin-2-one;8-(ethyl-propyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;8-(1-hydroxymethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(1-ethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-diethylamino-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(ethyl-propyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-hydroxymethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(1-hydroxymethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(1-ethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-diethylamino-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(ethyl-propyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;4-(butyl-ethyl-amino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-hydroxymethyl-propoxy)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-hydroxymethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(1-ethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-diethylamino-5-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;5-(ethyl-propyl-amino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;8-(butyl-ethyl-amino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;4-(2,4-dichlorophenyl)-5-methyl-2-[N-(1-(methoxymethyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole; oxalate of4-(2,4-dichlorophenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methylisoquinol-5-yl)-N-propylamino]thiazole;4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-methoxycarbonylmethylindol-5yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-chloroisoquinol-5-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-1-methoxynaphth-2-yl)-N-propylamino]thiazole;oxalate of4-(2-chloro-4-trifluoromethylphenyl)-5-methyl-2-[N-6-methoxyisoquinol-5-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(2-ethoxynaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2[N-(2,3-dimethylnaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(6-bromo-2-methoxynaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(2,6-dimethylnaphth-1-yl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-(methoxymethyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;chlorhydrate of4-(2-chloro-4-methoxyphenyl)-5-methyl-2-[N-(1-(cyclopropyl)-1-(naphth-2-yl)methyl)-N-propylamino]thiazole;3-(2,4-dichlorophenyl)-5-methyl-7(N-propyl-N-cyclopropanemethylamino)-pyrazolo[2,3-a]pyrimidine;3-(2,4-dichlorophenyl)-5-methyl-7-(N-allyl-N-cyclopropanemethylamino)-pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N,N-diallylamino)-pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N-butyl-N-cyclopropane-methyl-amino)pyrazolo[2,3-a]pyrimidine;2-methylthio-3-(2,4-dichlorophenyl)-5-methyl-7-(N-propyl-N-cyclopropane-methyl-amino)pyrazolo[2,3-a]pyrimidine;2-methyl-3-(4-chlorophenyl)-5-methyl-7-(N,N-dipropylamino)-pyrazolo[2,3-a]pyrimidine;3-[6-(dimethylamino)-3-pyridinyl]-2,5-dimethyl-N,N-dipropylpyrazolo[2,3-a]pyrimidin-7-amine;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidine-7-amine;3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo(2,3-a)pyrimidine;7-(N-diethylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine;7-(N-(3-cyanopropyl)-N-propylamino-2,5,dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]-pyrazolopyrimidine;[3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl]-(1-ethyl-propyl)-amine;[2-(4-chloro-2,6-dimethyl-phenoxy)-3,6-dimethyl-pyridin-4-yl]-(1-ethyl-propyl)-amine;cyclopropylmethyl-[3-(2,4-dimethyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;cyclopropylmethyl-[3-(2-methyl-4-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;cyclopropylmethyl-[3-(2,4-di-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;[3-(2-methyl-4-chloro-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-di-propyl-amine;[2,5-dimethyl-3-(2,4-dimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;[2,5-dimethyl-3-(2,4-dichloro-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;4-(1-ethyl-propylamino)-6-methyl-2-(2,4,6-trimethyl-phenoxy)-nicotinicacid methyl ester;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N-propyl-N-cyclopropylmethyl-pyrazolo[2,3-a]pyrimidin-7-amine;and3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N-ethyl-N-cyclopropylmethyl-pyrazolo[2,3-a]pyrimidin-7-amine.28. The kit of claim 27 wherein the corticotropin releasing factorantagonist is a compound selected from the group consisting of:4-(1-ethyl-propoxy)-3,6-dimethyl-2-(2,4,6-trimethylphenoxy)-pyridine;4-(1-ethylpropoxy)-2,5-dimethyl-6-(2,4,6-trimethylphenoxy)-pyrimidine;[4-(1-ethyl-propoxy)-3,6-dimethyl-pyridin-2-yl]-(2,4,6-trimethylphenyl)-amine;3-{(4-methyl-benzyl)-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amino}-propan-1-ol;propyl-ethyl-[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine;ethyl-n-propyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amine;2-{N-n-butyl-N-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}-ethanol;[3,6-dimethyl-1-(2,4,6-trimethylphenyl)-1H-pyrazolo[3,4,b]pyridin-4-yl]-(1-methoxymethylpropyl)-amine;4-(1-ethylpropoxy)-2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-b]pyridine;2,5,6-trimethyl-7-(1-propylbutyl)-4-(2,4,6-trimethylphenoxy)-7H-pyrrolo[2,3-d]pyrimidine;1-(1-ethylpropyl)-6-methyl-4-(2,4,6-trimethylphenoxy)-1,3-dihydro-imidazo[4,5-c]pyridin-2-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-pyrido[3,4-b]pyrazin-3-one;1-(1-ethyl-propyl)-4,7-dimethyl-5-(2,4,6-trimethyl-phenoxy)-1,2,3,4-tetrahydro-pyrido[3,4-b]pyrazine;1-(1-ethyl-propyl)-7-methyl-2-oxo-5-(2,4,6-trimethyl-phenoxy)-1,23,4-tetra-hydro-[1,6]naphthyridine-3-carboxylicacid isopropyl ester;1-(1-ethyl-propyl)-7-methyl-5-(2,4,6-trimethyl-phenoxy)-1,4-dihydro-2H-3-oxa-1,6-diaza-naphthalene;(1-ethyl-propyl)-[5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-amine;7-(1-ethyl-propoxy)-2,5-dimethyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine;4-(1-ethyl-propoxy)-2,5-dimethyl-7-(2,4,6-trimethyl-phenyl)-5H-pyrrolo[3,2-d]pyrimidine;4-(butyl-ethyl-amino)-2,6-dimethyl-8-(2,4,6-trimethyl-phenyl)-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one;8-(1-ethyl-propoxy)-6-methyl-4-(2,4,6-trimethyl-phenyl)-1,2,3,4-tetrahydro-pyrido[2,3-b]pyrazine;4-(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;(1-ethyl-propyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-quinolin-4-yl]-amine;(propyl-ethyl)-[2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido-[2,3-d]pyrimidin-4-yl]-amine;(1-ethyl-propoxy)-2-methyl-8-(2,4,6-trimethyl-phenyl)-5,6,7,8-tetrahydro-pyrido[2,3-d]pyrimidine;8-(1-hydroxymethyl-propylamino)-6-methyl-4-(2,4,6-trimethyl-phenyl)-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one;4-(1-hydroxymethyl-propylamino)-2-methyl-8-(2,4,6-trimethyl-phenyl)-quinoline;5-(1-hydroxymethyl-propylamino)-7-methyl-1-(2,4,6-trimethyl-phenyl)-1,4-dihydro-2H-3-oxa-1,8-diaza-naphthalene;[3,6-dimethyl-2-(2,4,6-trimethyl-phenoxy)-pyridin-4-yl]-(1-ethyl-propyl)-amine;cyclopropylmethyl-[3-(2,4-dimethyl-phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]-propyl-amine;[2,5-dimethyl-3-(2,4-dimethyl-phenyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-(1-ethyl-propyl)-amine;3-[6-(dimethylamino)-3-pyridinyl]-2,5-dimethyl-N,N-dipropylpyrazolo[2,3-a]pyrimidin-7-amine;3-[6-(dimethylamino)-4-methyl-3-pyridinyl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidine-7-amine;3-(2,4-dimethoxyphenyl)-2,5-dimethyl-7-(N-propyl-N-methyloxyethylamino)-pyrazolo(2,3-a)pyrimidine;7-(N-diethylamino)-2,5-dimethyl-3-(2-methyl-4-methoxyphenyl-[1,5-a]-pyrazolopyrimidine;and7-(N-(3-cyanopropyl)-N-propylamino-2,5,dimethyl-3-(2,4-dimethylphenyl)-[1,5-a]-pyrazolopyrimidine.29. The kit of claim 26 wherein the glucocorticoid receptor antagonistis a compound of formula IA

an isomer thereof, a prodrug of said compound or isomer, or apharmaceutically acceptable salt of said compound, isomer or prodrug;wherein m is 1 or 2; represents an optional bond; A is selected from thegroup consisting of

D is CR₇, CR₇R₁₆, N, NR₇ or O; E is C, CR₆or N; F is CR₄, CR₄R₅ or O; G,H and I together with 2 carbon atoms from the A-ring or 2 carbon atomsfrom the B-ring form a 5-membered heterocyclic ring comprising one ormore N, O or S atoms; provided that there is at most one of O and S perring; J, K, L and M together with 2 carbon atoms from the B-ring forms a6-membered heterocyclic ring comprising 1 or more N atoms; X is a)absent, b) —CH₂—, c) —CH(OH)— or d) —C(O)—; R₁ is a) —H, b) —Z—CF₃, c)—(C₁-C₆)alkyl, d) —(C₂-C₆)alkenyl, e) —(C₂-C₆)alkynyl, f) —CHO, g)—CH═N—OR₁₂, h) —Z—C(O)OR₁₂, i) —Z—C(O)—NR₁₂R₁₃, j) —Z—C(O)—NR₁₂—Z-het,k) —Z—NR₁₂R₁₃, l) —Z—NR₁₂het, m) —Z-het, n) —Z—O-het, o) —Z-aryl′, p)—Z—O-aryl′, q) —CHOH-aryl′ or r) —C(O)-aryl′ wherein aryl′ insubstituents o) to r) is substituted independently with 0, 1 or 2 of thefollowing: —Z—OH, —Z—NR₁₂R₁₃, —Z—NR₁₂-het, —C(O)NR₁₂R₁₃,—C(O)O(C₁-C₆)alkyl, —C(O)OH, —C(O)-het, —NR₁₂—C(O)—(C₁-C₆)alkyl,—NR₁₂—C(O)—(C₂-C₆)alkenyl, —NR₁₂—C(O)—(C₂-C₆)alkynyl, —NR₁₂—C(O)—Z-het,—CN, —Z-het, —O—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃,—O—(C₁-C₃)alkyl-C(O)O(C₁-C₆)alkyl, —NR₁₂—Z—C(O)O(C₁-C₆)alkyl,—N(Z—C(O)O(C₁-C₆)alkyl)₂, —NR₁₂—Z—C(O)—NR₁₂R₁₃, —Z—NR₁₂—SO₂—R₁₃,—NR₁₂—SO₂-het, —C(O)H, —Z—NR₁₂—Z—O(C₁-C₆)alkyl, —Z—NR₁₂—Z—NR₁₂R₁₃,—Z—NR₁₂—(C₃-C₆)cycloalkyl, —Z—N(Z—O(C₁-C₆)alkyl)₂, —SO₂R₁₂, —SOR₁₂,—SR₁₂, —SO₂NR₁₂R₁₃, —O—C(O)—(C₁-C₄)alkyl, —O—SO₂-(C₁-C₄)alkyl, -halo or—CF₃; Z for each occurrence is independently a) —(C₀-C₆)alkyl, b)—(C₂-C₆)alkenyl or c) —(C₂-C₆)alkynyl; R₂ is a) —H, b) -halo, c) —OH, d)—(C₁-C₆)alkyl substituted with 0 or 1—OH, e) —NR₁₂R₁₃, f)—Z—C(O)O(C₁-C₆)alkyl, g) —Z—C(O)NR₁₂R₁₃, h) —O—(C₁-C₆)alkyl, i)—Z—O—C(O)—(C₁-C₆)alkyl, j) —Z—O—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃, k)—Z—O—(C₁-C₃)alkyl-C(O)—O(C₁-C₆)alkyl, l) —O—(C₂-C₆)alkenyl, m)—O—(C₂-C₆)alkynyl, n) —O—Z-het, o) —COOH, p) —C(OH)R₁₂R₁₃ or q) —Z—CN;R₃ is a) —H, b) —(C₁-C₁₀)alkyl wherein 1 or 2 carbon atoms, other thanthe connecting carbon atom, may optionally be replaced with 1 or 2heteroatoms independently selected from S, O and N and wherein eachcarbon atom is substituted with 0, 1 or 2 R_(y), c) —(C₂-C₁₀)alkenylsubstituted with 0, 1 or 2 R_(y), d) —(C₂-C₁₀)alkynyl wherein 1 carbonatom, other than the connecting carbon atom, may optionally be replacedwith 1 oxygen atom and wherein each carbon atom is substituted with 0, 1or 2 R_(y), e) —CH═C═CH₂, f) —CN, g) —(C₃-C₆)cycloalkyl, h) —Z-aryl, i)—Z-het, j) —C(O)O(C₁-C₆)alkyl, k) —O(C₁-C₆)alkyl, l) —Z—S—R₁₂, m)—Z—S(O)—R₁₂, n) —Z—S(O)₂—R₁₂, o) —CF₃ p) —NR₁₂O-(C₁-C₆)alkyl or q)—CH₂OR_(y); provided that one of R₂ and R₃ is absent when there is adouble bond between CR₂R₃ (the 7 position) and the F moiety (the 8position) of the C-ring; R_(y) for each occurrence is independently a)—OH, b) -halo, c) —Z—CF₃, d) —Z—CF(C₁-C₃ alkyl)₂, e) —CN, f) —NR₁₂R₁₃,g) —(C₃-C₆)cycloalkyl, h) —(C₃-C₆)cycloalkenyl, i) —(C₀-C₃)alkyl-aryl,j) -het or k) —N₃; or R₂ and R₃ are taken together to form a) ═CHR₁₁, b)═NOR₁₁, c) ═O, d) ═N—NR₁₂, e) ═N—NR₁₂—C(O)—R₁₂, f) oxiranyl or g)1,3-dioxolan-4-yl; R₄ and R₅ for each occurrence are independently a)—H, b) —CN, c) —(C₁-C₆)alkyl substituted with 0 to 3 halo, d)—(C₂-C₆)alkenyl substituted with 0 to 3 halo, e) —(C₂-C₆)alkynylsubstituted with 0 to 3 halo, f) —O—(C₁-C₆)alkyl substituted with 0 to 3halo, g) —O—(C₂-C₆)alkenyl substituted with 0 to 3 halo, h)—O—(C₂-C₆)alkynyl substituted with 0 to 3 halo, i) halo, j) —OH, k)(C₃-C₆)cycloalkyl or l) (C₃-C₆)cycloalkenyl; or R₄ and R₅ are takentogether to form ═O; R₆ is a) —H, b) —CN, c) —(C₁-C₆)alkyl substitutedwith 0 to b 3 halo, d) —(C₂-C₆)alkenyl substituted with 0 to 3 halo, e)—(C₂-C₆)alkynyl substituted with 0 to 3 halo or f) —OH; R₇ and R₁₆ foreach occurrence are independently a) —H, b) -halo, c) —CN, d)—(C₁-C₆)alkyl substituted with 0 to 3 halo, e) —(C₂-C₆)alkenylsubstituted with 0 to 3 halo or f) —(C₂-C₆)alkynyl substituted with 0 to3 halo; provided that R₇ is other than —CN or -halo when D is NR₇; or R₇and R₁₆ are taken together to form ═O; R₈, R₉, R₁₄ and R₁₅ for eachoccurrence are independently a) —H, b) -halo, c) (C₁-C₆)alkylsubstituted with 0 to 3 halo, d) —(C₂-C₆)alkenyl substituted with 0 to 3halo, e) —(C₂-C₆)alkynyl substituted with 0 to 3 halo, f) —CN, g)—(C₃-C₆)cycloalkyl, h) —(C₃-C₆)cycloalkenyl, i) —OH, j) —O-(C₁-C₆)alkyl,k) —O—(C₁-C₆)alkenyl, l) —O—(C₁-C₆)alkynyl, m) —NR₁₂R₁₃, n) —C(O)OR₁₂ oro) —C(O)NR₁₂R₁₃; or R₈ and R₉ are taken together on the C-ring to form═O; provided that when m is 2, only one set of R₈ and R₉ are takentogether to form ═O; or R₁₄ and R₁₅ are taken together to form ═O;provided that when R₁₄ and R₁₅ are taken together to form ═O, D is otherthan CR₇ and E is other than C; R₁₀ is a) —(C₁-C₁₀)alkyl substitutedwith 0 to 3 substituents independently selected from -halo, —OH and —N₃,b) —(C₂-C₁₀)alkenyl substituted with 0 to 3 substituents independentlyselected from -halo, —OH and —N₃, c) —(C₂-C₁₀)alkynyl substituted with 0to 3 substituents independently selected from -halo, —OH and —N₃, d)-halo, e) —Z—CN, f) —OH, g) —Z-het, h) —Z—NR₁₂R₁₃, i) —Z—C(O)-het, j)—Z—C(O)—(C₁-C₆)alkyl, k) —Z—C(O)—NR₁₂R₁₃, l) —Z—C(O)—NR₁₂—Z—CN, m)—Z—C(O)—NR₁₂-Z-het, n) —Z—C(O)—NR₁₂—Z-aryl, o) —Z—C(O)—NR₁₂—Z—NR₁₂R₁₃,p) —Z—C(O)—NR₁₂—Z—O(C₁-C₆)alkyl, q) —(C₁-C₆)alkyl-C(O)OH, r)—Z—C(O)O(C₁-C₆)alkyl, s) —Z—O—(C₀-C₆)alkyl-het, t)—Z—O—(C₀-C₆)alkyl-aryl, u) —Z—O—(C₁-C₆)alkyl substituted with 0 to 2R_(x), v) —Z—O—(C₁-C₆)alkyl-CH(O), w) —Z—O—(C₁-C₆)alkyl-NR₁₂-het, x)—Z—O—Z-het-Z-het, y) —Z—O—Z-het-Z—NR₁₂R₁₃, z) —Z—O—Z-het-C(O)-het, a1)—Z—O—Z—C(O)-het, b1) —Z—O—Z—C(O)-het-het, C₁) —Z—O—Z—C(O)—(C₁-C₆)alkyl,d1) —Z—O—Z—C(S)—NR₁₂R₁₃, e1) —Z—O—Z—C(O)—NR₁₂R₁₃, f1)—Z—O—Z—(C₁-C₃)alkyl-C(O)—NR₁₂R₁₃, g1) —Z—O—Z—C(O)—O(C₁-C₆)alkyl, h1)—Z—O—Z—C(O)—OH, i1) —Z—O—Z—C(O)—NR₁₂—O(C₁-C₆)alkyl, j1)—Z—O—Z—C(O)—NR₁₂—OH, k1) —Z—O—Z—C(O)—NR₁₂—Z—NR₁₂R₁₃, l1)—Z—O—Z—C(O)—NR₁₂—Z-het, m1) —Z—O—Z—C(O)—NR₁₂—SO₂-(C₁-C₆)alkyl, n1)—Z—O—Z—C(═NR₁₂)(NR₁₂R₁₃), o1) —Z—O—Z—C(═NOR₁₂)(NR₁₂R₁₃), p1)—Z—NR₁₂—C(O)—O—Z—NR₁₂R₁₃, q1) —Z—S—C(O)—NR₁₂R₁₃, r1)—Z—O—SO₂—(C₁-C₆)alkyl, s1) —Z—O—SO₂-aryl, t1) —Z—O—SO₂—NR₁₂R₁₃, u1)—Z—O—SO₂—CF₃, v1) —Z—NR₁₂C(O)OR₁₃ or w1) —Z—NR₁₂C(O)R₁₃; or R₉ and R₁₀are taken together on the moiety of formula A-5 to form a) ═0 or b)═NOR₁₂; R₁₁ is a) —H, b) —(C₁-C₅)alkyl, c) —(C₃-C₆)cycloalkyl or d)—(C₀-C₃)alkyl-aryl; R₁₂ and R₁₃ for each occurrence are eachindependently a) —H, b) —(C₁-C₆)alkyl wherein 1 or 2 carbon atoms, otherthan the connecting carbon atom, may optionally be replaced with 1 or 2heteroatoms independently selected from S, O and N and wherein eachcarbon atom is substituted with 0 to 6 halo, c) —(C₂-C₆)alkenylsubstituted with 0 to 6 halo or d) —(C₁-C₆)alkynyl wherein 1 carbonatom, other than the connecting carbon atom, may optionally be replacedwith 1 oxygen atom and wherein each carbon atom is substituted with 0 to6 halo; or R₁₂ and R₁₃ are taken together with N to form het; or R₆ andR₁₄ or R₁₅ are taken together to form 1,3-dioxolanyl; aryl is a) phenylsubstituted with 0 to 3 R_(x), b) naphthyl substituted with 0 to 3 R_(x)or c) biphenyl substituted with 0 to 3 R_(x); het is a 5-,6- or7-membered saturated, partially saturated or unsaturated ring containingfrom one (1) to three (3) heteroatoms independently selected from thegroup consisting of nitrogen, oxygen and sulfur; and including anybicyclic group in which any of the above heterocyclic rings is fused toa benzene ring or another heterocycle; and the nitrogen may be in theoxidized state giving the N-oxide form; and substituted with 0 to 3R_(x); R_(x) for each occurrence is independently a) -halo, b) —OH, c)—(C₁-C₆)alkyl, d) —(C₂-C₆)alkenyl, e) —(C₂-C₆)alkynyl, f)—O(C₁-C₆)alkyl, g) —O(C₂-C₆)alkenyl, h) —O(C₂-C₆)alkynyl, i)—(C₀-C₆)alkyl-NR₁₂R₁₃, j) —C(O)—NR₁₂R₁₃, k) —Z—SO₂R₁₂, l)—Z—SOR₁₂, m)—Z—SR₁₂, n) —NR₁₂—SO₂R₁₃, o) —NR₁₂—C(O)—R₁₃, p) —NR₁₂-OR₁₃, q)—SO₂—NR₁₂R₁₃, r) —CN, s) —CF₃, t) —C(O)(C₁-C₆)alkyl, u) ═O, v)—Z—SO₂-phenyl or w) —Z—SO₂-het′; aryl′ is phenyl, naphthyl or biphenyl;het′ is a 5-,6- or 7-membered saturated, partially saturated orunsaturated ring containing from one (1) to three (3) heteroatomsindependently selected from the group consisting of nitrogen, oxygen andsulfur; and including any bicyclic group in which any of the aboveheterocyclic rings is fused to a benzene ring or another heterocycle;provided that: 1) X—R₁ is other than hydrogen or methyl; 2) when R₉ andR₁₀ are substituents on the A-ring, they are other than mono- ordi-methoxy; 3) when R₂ and R₃ are taken together to form ═CHR₁₁ or ═Owherein R₁₁ is —O(C₁-C₆)alkyl, then —X—R₁ is other than (C₁-C₄)alkyl; 4)when R₂ and R₃ taken together are C═O and R₉ is hydrogen on the A-ring;or when R₂ is hydroxy, R₃ is hydrogen and R₉ is hydrogen on the A-ring,then R₁₀ is other than —O—(C₁-C₆)alkyl or —O—CH₂-phenyl at the2-position of the A-ring; 5) when X—R₁ is (C₁-C₄)alkyl, (C₂-C₄)alkenylor (C₂-C₄)alkynyl, R₉ and R₁₀ are other than mono-hydroxy or ═O,including the diol form thereof, when taken together; and 6) when X isabsent, R₁ is other than a moiety containing a heteroatom independentlyselected from N, O or S directly attached to the juncture of the B-ringand the C-ring.
 30. The kit of claim 29 wherein the glucocorticoidreceptor antagonist is a compound selected from the group consisting of:2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)—N—(4-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-(2-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide, 4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)—N—(3-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-; carbamic acid, [2-(dimethylamino)ethyl]-,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-2-phenanthrenylester,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-N-pyrazinyl-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2-(1-propynyl)-7-(4-pyridinylmethoxy)-,[2R-(2α,4aα,10aβ)]; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-2-(1-propynyl)-7-(2-pyridinylmethoxy)-,[2R-(2α,4aα,10aβ)]; 2-phenanthrenecarbonitrile, 4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-(1-propynyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(1-propynyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide, 4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-propyl-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-4b-(phenylmethyl)-7-propyl-N-(2-pyridinylmethyl)-,[4bS-(4bα,7α,8aβ)]-; 2-phenanthrenol, 1,2,3,4,4a,9,10,10a-octahydro-4a-(phenylmethyl)-7-(3-pyridinylmethoxy)-2-(3,3,3-trifluoropropyl)-,[2S-(2α,4aα, 10aβ)]-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-7-[(2-methyl-3-pyridinyl)methoxy]-4a-(phenylmethyl)-2-(3,3,3-trifluoropropyl)-,[2S-(2α,4aα,10aβ)]-;2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(3,3,3-trifluoropropyl)-,(4bS,7S,8aR); 2-phenanthrenecarboxamide, 4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-7-methyl-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-,(4bS,7R,8aR)-; 2-phenanthrenecarboxamide,4b,5,6,7,8,8a,9,10-octahydro-7-hydroxy-7-methyl-4b-(phenylmethyl)-N-3-pyridinyl-,(4bS,7R,8aR)-; 2-phenanthrenol,1,2,3,4,4a,9,10,10a-octahydro-7-[(2-methyl-3-pyridinyl)methoxy]-4a-(phenylmethyl)-2-(trifluoromethyl)-,(2R,4aS, 10aR)-; and 2-phenanthrenecarboxamide, 4b, 5, 6, 7, 8, 8a, 9,10-octahydro-7-hydroxy-N-[(2-methyl-3-pyridinyl)methyl]-4b-(phenylmethyl)-7-(trifluoromethyl)-,(4bS, 7R, 8aR)-.